The canonical mechanism of OP neurotoxicity is inhibition of acetylcholinesterase (AChE). Organophosphates (OPs) are a group of synthetic compounds that are neurotoxic in humans and preclinical models. Lein, in Advances in Neurotoxicology, 2019 Abstract PEG conjugated serine is very biocompatible with low toxicity and can reduce the acute toxicity of DZ as a new combination therapy.Michelle Guignet, Pamela J. Cholinesterase enzyme activity, lipid peroxidation, and mitochondrial function significantly improved through PEG-NPs when compared with the DZ group.

Percentage of surviving significantly improved by 12.5, 25, and 25% through the usage of PEG-NPs at doses of 100, 200, and 400 mg/kg, respectively, when compared with the DZ group.

The hemolysis of the PEG-NPs was calculated at 0.867%, 50 % inhibitory concentration (IC 50) was calculated 36 ± 4.5, and 41 ± 3.4 mg/mL on SK-BR-3 and HFFF2 cell lines, respectively. NMR and IR data confirmed that the conjugation of PEG to serine occurred successfully. Atropine (20 mg/kg, i.p.) with pralidoxime (20 mg/kg, i.p.) was used as the standard therapy compared to PEG-NPs. PEG-NPs were administered (i.p.) 20 min after a single dose of DZ (LD 50 166 mg/kg). In vivo studies of PEG-NPs were evaluated on DZ-exposed mice. In vitro studies, including hemolysis assay and cytotoxicity on SK-BR-3 and HFFF2 cell lines, were performed. PEG-serine NPs (PEG-NPs) were purified and their structure was analyzed by 1H NMR, 13 C NMR, IR, and particle size was determined via dynamic light scattering. Serine and PEG were conjugated with a reductive amination reaction. In this study, serine was attached to the polyethylene glycol-bisaldehyde (PEG) as a novel antidote for diazinon (DZ) poisoning. Acute organophosphate pesticide poisoning causes considerable worldwide mortality and morbidity.

Organophosphate antidote