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Anticholinesterase insecticide retrospective.

ABSTRACT: The anticholinesterase (antiChE) organophosphorus (OP) and methylcarbamate (MC) insecticides have been used very effectively as contact and systemic plant protectants for seven decades. About 90 of these compounds are still in use - the largest number for any insecticide chemotype or mode of action. In both insects and mammals, AChE inhibition and acetylcholine accumulation leads to excitation and death. The cholinergic system of insects is located centrally (where it is protected from ionized OPs and MCs) but not at the neuromuscular junction. Structural differences between insect and mammalian AChE are also evident in their genomics, amino acid sequences and active site conformations. Species selectivity is determined in part by inhibitor and target site specificity. Pest population selection with OPs and MCs has resulted in a multitude of modified AChEs of altered inhibitor specificity some conferring insecticide resistance and others enhancing sensitivity. Much of the success of antiChE insecticides results from a suitable balance of bioactivation and detoxification by families of CYP450 oxidases, hydrolases, glutathione S-transferases and others. Known inhibitors for these enzymes block detoxification and enhance potency which is particularly important in resistant strains. The current market for OPs and MCs of 19% of worldwide insecticide sales is only half of that of 10 years ago for several reasons: there have been no major new compounds for 30 years; resistance has eroded their effectiveness; human toxicity problems are still encountered; the patents have expired reducing the incentive to update registration packages; alternative chemotypes or control methods have been developed. Despite this decline, they still play a major role in pest control and the increasing knowledge on their target sites and metabolism may make it possible to redesign the inhibitors for insensitive AChEs and to target new sites in the cholinergic system. The OPs and MCs are down but not out.

SUBMITTER: Casida JE

PROVIDER: S-EPMC3572339 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Anticholinesterase insecticide retrospective.

Casida John E JE Durkin Kathleen A KA

Chemico-biological interactions 20120816 1

The anticholinesterase (antiChE) organophosphorus (OP) and methylcarbamate (MC) insecticides have been used very effectively as contact and systemic plant protectants for seven decades. About 90 of these compounds are still in use - the largest number for any insecticide chemotype or mode of action. In both insects and mammals, AChE inhibition and acetylcholine accumulation leads to excitation and death. The cholinergic system of insects is located centrally (where it is protected from ionized O ...[more]

PMID: 22926007

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Project description:ObjectiveTo develop a convenient nomogram for the bedside evaluation of patients with acute organophosphorus poisoning (AOPP).DesignThis was a retrospective study.SettingTwo independent hospitals in northern China, the First Hospital of Jilin University and the Lequn Hospital of the First Hospital of Jilin University.ParticipantsA total of 1657 consecutive patients admitted for the deliberate oral intake of AOPP within 24 hours from exposure and aged >18 years were enrolled between 1 January 2013 and 31 December 2018. The exclusion criteria were: normal range of plasma cholinesterase, exposure to any other type of poisonous drug(s), severe chronic comorbidities including symptomatic heart failure (New York Heart Association III or IV) or any other kidney, liver and pulmonary diseases. Eight hundred and thirty-four patients were included.Primary outcome measureThe existence of severely poisoned cases, defined as patients with any of the following complications: cardiac arrest, respiratory failure requiring ventilator support, hypotension or in-hospital death.Results440 patients from one hospital were included in the study to develop a nomogram of severe AOPP, whereas 394 patients from the other hospital were used for the validation. Associated risk factors were identified by multivariate logistic regression. The nomogram was validated by the area under the receiver operating characteristic curve (AUC). A nomogram was developed with age, white cells, albumin, cholinesterase, blood pH and lactic acid levels. The AUC was 0.875 (95% CI 0.837 to 0.913) and 0.855 (95% CI 0.81 to 0.9) in the derivation and validation cohorts, respectively. The calibration plot for the probability of severe AOPP showed an optimal agreement between the prediction by nomogram and actual observation in both derivation and validation cohorts.ConclusionA convenient severity evaluation nomogram for patients with AOPP was developed, which could be used by physicians in making clinical decisions and predicting patients' prognosis.

Project description:BackgroundTrichilia catigua A. Juss. (Meliaceae) is a species known as catuaba and used in folk medicine for the treatment of fatigue, stress, impotence and memory deficit. The main phytochemical compounds identified in the barks of T. catigua are flavalignans, flavan-3-ols and flavonoids which are associated with its antioxidant activity. Pre-clinical studies with T. catigua extracts have identified many pharmacological properties, such as anti-inflammatory, antidepressant, antinociceptive, pro-memory and neuroprotective against ischemia and oxidative stress. This study was designed in order to compare the chemical composition and in vitro antioxidant and anticholinesterase activity of four different polarity extracts and selected the one most active for in vivo studies in rodent models of stress, fatigue and memory.MethodsHexane, chloroform, hydroalcoholic and aqueous extracts from bark of Trichilia catigua were analyzed by RPHPLC-DAD-ESI-MS/MS. Antioxidant activity was assessed by 2,2-diphenyl-1-picryl hydrazyl (DPPH) assay and acetylcholinesterase inhibition by Ellman's modified method. In vivo studies (stress, fatigue and memory) were carried out with adult male mice and rats treated with hydroalcoholic extract in doses of 25-300 mg/kg (p.o.).ResultsWe confirmed the presence of cinchonain IIa, Ia and Ib, as main constituents in the four extracts, while procyanidins were detected only in hydroalcoholic extract. Antioxidant and anticholinesterase activity were observed for all extracts, with most potent activity found on the hydroalcoholic extract (EC50 = 43 μg/mL and IC50 = 142 μg/mL for DPPH scavenger and acetylcholinesterase inhibition, respectively). The treatment of laboratory animals with hydroalcoholic extract did not protect rats from cold immobilization stress and did not prevent the scopolamine-induced amnesia in mice. However, the treatment of mice with the hydroalcoholic extract partially reduced the fatigue induced by treadmill, since the highest dose increased the spontaneous locomotor activity and reduced the deficit on grip strength after the forced exercise (p < 0.05), in some observation times.ConclusionsThese data suggest the hydroalcoholic extract as the most suitable for plant extraction and partially support the folk use of T. catigua as antifatigue drug. . Trichilia catigua hydroalcoholic extract exhibits antioxidant and anticholinesterase activity in vitro and reduces the fatigue induced by forced exercise.

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Anticholinesterase insecticide retrospective.

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Anticholinesterase insecticide retrospective.

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