Organophosphates poisoning

The aerotoxic syndrome has been associated with exposure to tricresyl phosphate (TCP), which is used as additive in hydraulic fluids and engine lubricants. The toxic metabolite 2-(2-cresyl)-4H-1,3,2-benzodioxaphosphorin-2-oxide (CBDP) is formed from the TCP isomer tri-ortho-cresyl phosphate (TOCP) in vivo and is known to react with the active site serine in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) resulting in the inhibition of the enzymes. Previous in vitro studies showed pronounced species differences in the inhibition kinetics of cholinesterases by organophosphorus compounds (OP), which must be considered in the development of relevant animal models for the investigation of OP poisoning and the aerotoxic syndrome...

Organophosphorus compounds (OP) are highly toxic pesticides and nerve agents widely used in agriculture and chemical warfare. The extensive use of these chemicals has severe environmental implications, such as contamination of soil, water bodies, and food chains, thus endangering ecosystems and biodiversity. Plants absorb pesticide residues, which then enter the food chain and accumulate in the body fat of both humans and animals. Numerous human cases of OP poisoning have been linked to both acute and long-term exposure to these toxic OP compounds...

VX is an organophosphate acetylcholinesterase (AChE) inhibitor and while it is one of the most toxic AChE inhibitors known the extent of metabolism in humans is not currently well understood. The known metabolism in humans is limited to the metabolite identification from a single victim of the Osaka poisoning in 1994, which allowed for the identification of several metabolic products. VX has been reported to be metabolized in vitro by paraoxonase-1 and phosphotriesterase, although their binding constants are many orders of magnitude above the LD50 , suggesting limited physiological relevance...

Chemical warfare nerve agents and pesticides, known as organophosphorus compounds inactivate cholinesterases (ChEs) by phosphorylating the serine hydroxyl group located at the active site of ChEs. Over the course of time, phosphorylation is followed by loss of an organophosphate-leaving group and the bond with ChEs becomes irreversible, a process known as aging. Differently, structurally related irreversible catalytic poisons bearing sulfur instead of phosphorus convert ChEs in its aged form only by covalently binding to the key catalytic serine...

Organophosphorus agents are easily absorbed via respiratory, gastrointestinal, and dermal routes, and inhibit the acetylcholine transferase enzyme (AChE), which is responsible for the majority of toxicity caused by organophosphates in the body. A comprehensive search was conducted across three prominent databases, namely Google Scholar, PubMed, and Science Direct, to identify relevant articles published. The search focused on the keywords "MgSO4" or "magnesium sulfate" in conjunction with "organophosphate" or "organophosphate poisoning...

Organophosphorus poisoning is a critical condition that can cause central nervous system depression, respiratory failure, and death early on. As its clinical manifestations closely resemble those of carbamate pesticide poisoning, the aim of this case study is to present a case of misdiagnosis, initially identifying carbofuran poisoning as organophosphate in a patient suspect of a heatstroke. We also present a case of intentional self-poisoning with organophosphate dichlorvos to underline the likelihood of pesticide poisoning in patients exhibiting acute cholinergic symptoms when the ingested substance is not known...

Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being replaced in many guidelines by midazolam, which terminates seizures more quickly, particularly when administered intramuscularly...

Organophosphate poisoning is a significant global health concern with implications for both occupational and environmental settings. This comprehensive review thoroughly explores the biochemical basis, clinical presentation, diagnostic methods, treatment strategies, and long-term effects of organophosphate exposure. The acute phase is characterized by cholinergic crisis, respiratory distress, and neurological manifestations, while delayed complications include the intermediate syndrome and organophosphate-induced delayed neuropathy...

The H1 -antihistamine diphenhydramine antagonizes cholinesterase inhibitor poisoning in various animal species. One aspect of acute antidotal actions of diphenhydramine is increasing the median lethal doses (LD50) of toxicants. The objective of this meta-analysis was to assess the antidotal action of diphenhydramine against short-term toxicity (LD50) of cholinesterase inhibitors in experimental animals. The experimental studies selected were according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines...

In India, organophosphorus (OP) chemicals known as anticholinesterases cause a considerable amount of disease and mortality. While precise figures are unavailable, data from hospitals indicates that about 50% of acute poisoning episodes are attributed to organophosphates. Anticholinesterases, when accidentally or suicidally exposed, cause three different neurological disorders. The first is an acute cholinergic crisis that can be fatal and necessitates administration in an intensive care unit; the second is an intermediate syndrome that frequently results in cranial nerve palsies, proximal and respiratory muscle weakness, and respiratory support for patients; and the third is a delayed organophosphate-induced polyneuropathy...

Current treatments against organophosphate poisoning (OPP) do not directly address effects mediated by the overstimulation of nicotinic acetylcholine receptors (nAChR). Non-oxime bispyridinium compounds (BPC) promote acetylcholine esterase-independent recovery of organophosphate-induced paralysis. Here, we test the hypothesis that they act by positive modulatory action on nAChRs. Using two-electrode voltage clamp analysis in combination with mutagenesis and molecular docking analysis, the potency and molecular mode of action of a series of nine BPCs was investigated on human α7 and muscle-type nAChRs expressed in Xenopus laevis oocytes...

INTRODUCTION: Organophosphorus poisoning (OPP) stands as a significant health concern in numerous regions, especially in developing nations. Despite the rising complexities and case fatalities associated with exposure, the treatment approach has remained unchanged for many years. Based on clinical insights, certain pharmacologic agents have demonstrated utility in enhancing outcomes and reducing complications arising from this type of exposure. OBJECTIVES: The objective of this study is to compare the outcome of N-acetyl cysteine in the treatment of acute organophosphate poisoning cases...

Intoxications with organophosphorus compounds (OPCs) effect a severe impairment of cholinergic neurotransmission that, as a result of overstimulation may lead to desensitization of nicotinic acetylcholine receptors (nAChRs) and finally to death due to respiratory paralysis. So far, therapeutics, that are capable to address and revert desensitized neuromuscular nAChRs into their resting, i.e. functional state are still missing. Still, among a class of compounds termed bispyridinium salts, which are characterized by the presence of two pyridinium subunits, constituents have been identified, that can counteract organophosphate poisoning by resensitizing desensitized nAChRs...

Pralidoxime is the only oxime antidote to organophosphate poisoning stocked in the United Kingdom, produced by rational drug design in the 1950s. Typically, it is used alongside atropine, to reverse the effects of acetylcholinesterase inhibition. However, its efficacy has been questioned by recent meta-analyses of use treating attempted suicides in less economically developed countries, where organophosphate poisoning is more common. This policy analysis assesses the likely efficacy of pralidoxime in the United Kingdom, in scenarios largely different from those evaluated in meta-analyses...

Organophosphate poisoning is a common, under-reported cause of attempted and completed suicide worldwide. Following the resolution of the acute cholinergic syndrome, patients may develop respiratory muscle and proximal limb weakness, known as intermediate syndrome. A young man was brought to our rural hospital unconscious, in extremis, due to organophosphate pesticide poisoning. He developed atypical intermediate syndrome with global paralysis, persistent fasciculations and prolonged cholinergic symptoms, differing from the recognised presentation...

Organophosphate insecticide spray poses potential threat of contamination of environmental components their accumulation in aquatic organisms. Although various physiological deficits associated with their exposure in fishes are documented, yet their retention in their edible muscle tissues has been poorly studied. In this context, the study was undertaken to ascertain the bioaccumulation of two organophosphate insecticide compounds (dimethoate and chlorpyrifos) in the muscles of juvenile Cyprinus carpio . The study could provide insight into the risks to human health associated with consuming contaminated fish flesh...

The high-level toxic effects of organophosphate (OP) nerve agents severely threaten national security and public health. Generating trustworthy, accurate methods for quickly identifying these poisonous chemicals is urgently necessary. In this study, we have presented an azine-based colorimetric sensor (HBD) for the highly sensitive and selective identification of poisonous sarin gas surrogate diethylchlorophosphate (DCP). Our introduced sensor shows a purple color in contact with DCP, which is fully reversible upon the addition of triethylamine (TEA)...

BACKGROUND: Chlorpyrifos (CPF) is an organophosphate pesticide that inhibits acetylcholinesterase (AChE) activity. Investigations have also focused on its neurotoxicity, which is independent of AChE inhibition. Here, we evaluated the effect of CPF on oxidative indices in the brain tissue and explored the protective effect of curcumin (Cur) against its toxicity. METHODS: Forty male Wistar rats were divided into five groups, each consisting of eight rats (n = 8) per group...

Acute poisonings are a global public health problem, which implies costs and disease burden for society. In Colombia, there is a significant underreporting of data on acute poisoning and data gaps on the toxicological profile of the population. This study aims to identify the epidemiology of acute poisoning in a high-complexity hospital in southwestern Colombia. A descriptive study with retrospective data collection was performed. The variables were expressed through the measure of central tendency and dispersion...

Organophosphate (OP) toxicity is related to inhibition of acetylcholinesterase (AChE) activity, which plays a key role in the neurotransmission process. In this work, we report the ability of different zinc zeolitic imidazolate frameworks (ZIFs) to behave as potential antidotes against OP poisoning. The Zn-L coordination bond (L = purine, benzimidazole, imidazole, or 2-methylimidazole) is sensitive to the G-type nerve agent model compounds diisopropylfluorophosphate (DIFP) and diisopropylchlorophosphate, leading to P-X (X = F or Cl) bond breakdown into nontoxic diisopropylphosphate...