The mechanistic basis for the toxicity difference between juvenile rats and mice following exposure to the agricultural insecticide chlorpyrifos

Sette, Katelyn N; Alugabelly, Navatha; Glenn, Lauren B; Guo‐Ross, Shirley X.; Parkes, M Katherine; Wilson, Juliet R; Seay, Caitlin N; Carr, Russell L.

doi:10.1016/j.tox.2022.153317

Cited by 6 publications

(2 citation statements)

References 42 publications

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“…A large number of neurotropic substances are known to have a toxic effect on the central nervous system (CNS) due to a violation of the catalytic function of acetylcholinesterase (AChE) [1,2]. The AChE rapidly hydrolyzes an excess of the neurotransmitter acetylcholine preventing its accumulation in cholinergic synapses, thus providing a balance between the inhibition and excitation processes.…”

Section: Introductionmentioning

confidence: 99%

Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes

et al. 2022

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Chitosan-decorated liposomes were proposed for the first time for the intranasal delivery of acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) to the brain as a therapy for organophosphorus compounds (OPs) poisoning. Firstly, the chitosome composition based on phospholipids, cholesterol, chitosans (Cs) of different molecular weights, and its arginine derivative was developed and optimized. The use of the polymer modification led to an increase in the encapsulation efficiency toward rhodamine B (RhB; ~85%) and 2-PAM (~60%) by 20% compared to conventional liposomes. The formation of monodispersed and stable nanosized particles with a hydrodynamic diameter of up to 130 nm was shown using dynamic light scattering. The addition of the polymers recharged the liposome surface (from −15 mV to +20 mV), which demonstrates the successful deposition of Cs on the vesicles. In vitro spectrophotometric analysis showed a slow release of substrates (RhB and 2-PAM) from the nanocontainers, while the concentration and Cs type did not significantly affect the chitosome permeability. Flow cytometry and fluorescence microscopy qualitatively and quantitatively demonstrated the penetration of the developed chitosomes into normal Chang liver and M-HeLa cervical cancer cells. At the final stage, the ability of the formulated 2-PAM to reactivate brain AChE was assessed in a model of paraoxon-induced poisoning in an in vivo test. Intranasal administration of 2-PAM-containing chitosomes allows it to reach the degree of enzyme reactivation up to 35 ± 4%.

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Section: Introductionmentioning

confidence: 99%

Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes

et al. 2022

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“…In recent years, domestic and foreign studies have concentrated on the aging process and spontaneous reactivation of AChE in mammalians (e.g., mice, human blood, rabbits, zebrafish, etc.) inhibited by OPs [ 21 , 22 , 23 ]. Several important achievements with a significant reference value have been reported in these studies.…”

Section: Introductionmentioning

confidence: 99%

Study on Spontaneous Reactivation and Aging of Acetylcholinesterase Inhibited by Paraoxon and Malaoxon in Ten Species

Gao,

Ni,

et al. 2023

IJMS

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Organophosphorus insecticides (OPs), acting as serine phosphorylating agents in acetylcholinesterase (AChE), are highly effective neurotoxic insecticides. In our previous research, we found that six herbivorous pests and four ladybirds howed significantly higher AChE LC50 values than seven parasitoids and a predator (Epistrophe balteate), and that there was a significant correlation with the corresponding bimolecular rate constant (Ki) value. The Ki value of pests was much smaller than that of natural enemies and had a higher LC50 value.Then, we speculated that the low sensitivity of the pest AChE to OPs may be associated with its higher recovery and lower aging ability. In this work, the I50 and I90 were calculated, to determine the sensibility of AChE in ten representative species, including Plutella xylostella, Prodenia litura, Musca domestica, and Cavia porcellus, to paraoxon and malaoxon. The enzyme activities were measured at various time points, and kinetic calculations were used to obtain their spontaneous reactivation (Ks) and aging (Ka) constants, which were comprehensively compared. We conclude that the Ka and Ks of the AChE inhibited by OPs showed primarily species-specific correlations, and little correlation with the sensitivity to OPs. The differences in the AChE sensitivity to paraoxon among the ten species were much greater than in the sensitivity to malaoxon. Compared to paraoxon, malaoxon was more selective for Cavia porcellus. Coleoptera insects showed a stronger dephosphorylation ability than other insect groups. The recovery ability of phospho-AChE was stronger in mammals than in insects, which could be related to the low sensitivity of the AChE site of action to OPs. The Ka of the AChE inhibited by malaoxon was larger than that inhibited by paraoxon with the corresponding biomaterials, indicating that the OP type had a substantial relationship with the Ka of the AChE. We further discovered that, when insects were inhibited by OP, the tendency of AChE to undergo aging was greater than that of dephosphorylation. Overall, the study provides valuable information on the action mechanism of various OPs on AChE in several species, which could be used to further research into AChE and the potential dangers that organophosphates pose to animals.

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Cnr1−/− has minimal impact on chlorpyrifos-mediated effects in the mouse endocannabinoid system, but it does alter lipopolysaccharide-induced cytokine levels in splenocytes

Szafran

Nichols

Nicaise

et al. 2023

Chemico-Biological Interactions

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The mechanistic basis for the toxicity difference between juvenile rats and mice following exposure to the agricultural insecticide chlorpyrifos

Cited by 6 publications

References 42 publications

Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes

Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes

Study on Spontaneous Reactivation and Aging of Acetylcholinesterase Inhibited by Paraoxon and Malaoxon in Ten Species

Cnr1−/− has minimal impact on chlorpyrifos-mediated effects in the mouse endocannabinoid system, but it does alter lipopolysaccharide-induced cytokine levels in splenocytes

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