Management of Organophosphorus Poisoning

Aman, Sakib; Paul, Shrebash; Chowdhury, Fazle Rabbi

doi:10.1016/j.ccc.2021.03.011

Cited by 19 publications

(21 citation statements)

References 58 publications

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“…Using this concentration, we found that 67% (16/24) of animals survived 24 h after DFP exposure. In contrast, standard treatments ( Hulse et al, 2019 ; Alozi and Rawas-Qalaji, 2020 ; Aman et al, 2021 ) delivered coincident with DFP almost fully eliminated lethality. This included the muscarinic antagonist Atropine (3 mg/Kg), which promoted 94% (16/17) survival, and the acetylcholinesterase reactivator HI6 (50 mg/Kg), which caused 100% (16/16) survival.…”

Section: Resultsmentioning

confidence: 84%

“…Effects of organophosphate toxicity on respiration has been well-documented ( Hulse et al, 2014 ), and indeed respiratory failure is proposed to be a cause of organophosphate mortality ( Hulse et al, 2019 ; Aman et al, 2021 ). Therefore, we examined the effect of DFP and treatments on mouse respiratory mechanics using identical timelines and drug concentrations as used in the EEG studies.…”

Section: Resultsmentioning

confidence: 99%

“…There are numerous health effects of organophosphate toxicity that are physiologically related to activation of peripheral muscarinic and nicotinic acetylcholine receptors. These include bronchoconstriction and bronchorrhea, muscle tremors and fasciculations, bradycardia, and vomiting ( Alozi and Rawas-Qalaji, 2020 ; Aman et al, 2021 ). Central nervous system effects include respiratory depression, depressed consciousness, and seizures ( Reji et al, 2016 ; Williamson et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Current mainstay of therapy for organophosphate poisoning is the muscarinic acetylcholine receptor antagonist atropine. Antagonism of muscarinic receptors is known to decrease exocrine and respiratory secretions, reduce bronchospasms, prevent bradycardia, and protect against cholinergic seizures ( Carpentier et al, 2000 ; Aman et al, 2021 ). In addition, therapeutics that directly target organophosphate mechanisms are reactivators of acetylcholinesterase.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Sublethal Organophosphate Toxicity and Anti-cholinergics on Electroencephalogram and Respiratory Mechanics in Mice

Bugay¹,

Gregory²,

Belanger-Coast³

et al. 2022

Front. Neurosci.

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Organophosphates are used in agriculture as insecticides but are potentially toxic to humans when exposed at high concentrations. The mechanism of toxicity is through antagonism of acetylcholinesterase, which secondarily causes excess activation of cholinergic receptors leading to seizures, tremors, respiratory depression, and other physiological consequences. Here we investigated two of the major pathophysiological effects, seizures and respiratory depression, using subcutaneous injection into mice of the organophosphate diisopropylfluorophosphate (DFP) at sublethal concentrations (2.1 mg/Kg) alone and co-injected with current therapeutics atropine (50 mg/Kg) or acetylcholinesterase reactivator HI6 (3 mg/Kg). We also tested a non-specific cholinergic antagonist dequalinium chloride (2 mg/Kg) as a novel treatment for organophosphate toxicity. Electroencephalogram (EEG) recordings revealed that DFP causes focal delta frequency (average 1.4 Hz) tonic spikes in the parietal region that occur transiently (lasting an average of 171 ± 33 min) and a more sustained generalized theta frequency depression in both parietal and frontal electrode that did not recover the following 24 h. DFP also caused behavioral tremors that partially recovered the following 24 h. Using whole body plethysmography, DFP revealed acute respiratory depression, including reduced breathing rates and tidal volumes, that partially recover the following day. Among therapeutic treatments, dequalinium chloride had the most potent effect on all physiological parameters by reducing acute EEG abnormalities and promoting a full recovery after 24 h from tremors and respiratory depression. Atropine and HI6 had distinct effects on EEGs. Co-treatment with atropine converted the acute 1.4 Hz tonic spikes to 3 Hz tonic spikes in the parietal electrode and promoted a partial recovery after 24 h from theta frequency and respiratory depression. HI6 fully removed the parietal delta spike increase and promoted a full recovery in theta frequency and respiratory depression. In summary, while all anticholinergic treatments promoted survival and moderated symptoms of DFP toxicity, the non-selective anti-cholinergic dequalinium chloride had the most potent therapeutic effects in reducing EEG abnormalities, moderating tremors and reducing respiratory depression.

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Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Sublethal Organophosphate Toxicity and Anti-cholinergics on Electroencephalogram and Respiratory Mechanics in Mice

Bugay¹,

Gregory²,

Belanger-Coast³

et al. 2022

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…OPs act by inhibiting the activity of acetylcholinesterase (AChE) enzymes, leading to muscular dysfunction in target organisms [6]. Nevertheless, due to similarities in the AChE family among diverse groups of organisms, OPs also pose a risk to non-target animals, including humans [7,8]. The neurotoxic action in children is of special concern to the whole of society, as children are generally more vulnerable because their brains are still developing.…”

Section: Introductionmentioning

confidence: 99%

A FRET Approach to Detect Paraoxon among Organophosphate Pesticides Using a Fluorescent Biosensor

Rodrigues

Barbieri

Chino

et al. 2022

Sensors

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The development of faster, sensitive and real-time methods for detecting organophosphate (OP) pesticides is of utmost priority in the in situ monitoring of these widespread compounds. Research on enzyme-based biosensors is increasing, and a promising candidate as a bioreceptor is the thermostable enzyme esterase-2 from Alicyclobacillus acidocaldarius (EST2), with a lipase-like Ser–His–Asp catalytic triad with a high affinity for OPs. This study aimed to evaluate the applicability of Förster resonance energy transfer (FRET) as a sensitive and reliable method to quantify OPs at environmentally relevant concentrations. For this purpose, the previously developed IAEDANS-labelled EST2-S35C mutant was used, in which tryptophan and IAEDANS fluorophores are the donor and the acceptor, respectively. Fluorometric measurements showed linearity with increased EST2-S35C concentrations. No significant interference was observed in the FRET measurements due to changes in the pH of the medium or the addition of other organic components (glucose, ascorbic acid or yeast extract). Fluorescence quenching due to the presence of paraoxon was observed at concentrations as low as 2 nM, which are considered harmful for the ecosystem. These results pave the way for further experiments encompassing more complex matrices.

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Sublingual administration of atropine eye drops for treating organophosphorus poisoning

Hirayama,

Kamijo,

Nonaka

et al. 2024

Clinical Case Reports

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Management of Organophosphorus Poisoning

Cited by 19 publications

References 58 publications

Effects of Sublethal Organophosphate Toxicity and Anti-cholinergics on Electroencephalogram and Respiratory Mechanics in Mice

Effects of Sublethal Organophosphate Toxicity and Anti-cholinergics on Electroencephalogram and Respiratory Mechanics in Mice

A FRET Approach to Detect Paraoxon among Organophosphate Pesticides Using a Fluorescent Biosensor

Sublingual administration of atropine eye drops for treating organophosphorus poisoning

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