Identification of differentially expressed proteins related to organophosphorus‐induced delayed neuropathy in the brains of hens

Abstract

Some organophosphorus compounds can cause organophosphate-induced delayed neuropathy (OPIDN). Incidents have been documented for decades, however, little is known about which proteins contribute to the initiation, progression and development of OPIDN. In this study, 51 hens were divided into three groups. The tri-ortho-cresyl-phosphate (TOCP) group was treated with 1000 mg kg(-1) TOCP whereas the control group was treated with an equivalent volume of vehicle. The PMSF + TOCP group was treated subcutaneously with 40 mg kg(-1) phenylmethylsulfonyl fluoride (PMSF), followed by 1000 mg kg(-1) TOCP 24 h later. Proteins in the brains of hens were separated by two-dimensional polyacrylamide gel electrophoresis on day 5 after TOCP administration. Mass spectrometry identified eight differentially expressed proteins. Among these proteins, downregulated expression of glutamine synthetase (GS) in the brains of hens after TOCP treatment was further confirmed by real time RT-PCR and ELISA. Moreover, the brains of hens exposed to TOCP exhibited increased levels of glutamate (Glu) and cytosolic calcium concentration ([Ca(2+)](i)), and a decreased level of glutamine (Gln). However, there were no significant differences in GS expression or levels of Glu, Gln, and [Ca(2+)](i) in the brains of hens among the groups on day 21 after TOCP administration. These results indicate that TOCP exposure downregulates GS expression in the brains of hens, and that downregulation of GS is accompanied by increased levels of Glu and [Ca(2+)](i) in the early stage after TOCP administration. It is also suggested that the downregulated expression of GS might be associated with OPIDN through the disruption of homeostasis of the Glu-Gln cycle and [Ca(2+) ](i).

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

“…TOCP has been shown to bind to neuropathy target esterase (NTE) and leads to aging reaction of NTE, thereby inhibits its enzymatic activity, which is associated with the initiation, progression and development of OPIDN [35]. Jiang et al [2] reported that the down-regulated expression of glutamine synthetase (GS) might be associated with the delayed neuropathy induced by TOCP through the disruption of homeostasis of the glutamate (Glu)-glutamine (Gln) cycle and cytosolic calcium concentration. Zou et al [32] found that the delayed neuropathy induced by TOCP might be mediated by the activation of mitochondrial apoptotic pathway.…”

“…So adult hens are usually used as the animal model of OPIDN. Numerous studies show that the animal models of OPIDN have been successfully established in hens [2,[8][9][10][11].…”

“…Acute toxicity of OPs are well known, but some OPs, such as tri-orthocresyl phosphate (TOCP), can cause toxic neuropathy known as organophosphate-induced delayed neuropathy (OPIDN) in humans and sensitive animal species [2]. OPIDN often occurs 2-3 weeks after exposure of Ops.…”

Sarin (GB, O-isopropyl methylphosphonofluoridate) neurotoxicity: critical review

“…The study used hens treated with chlorpyrifos (CPF) and demonstrated signs of delayed neurotoxicity including NTE inhibition, CI inhibition and decreased ATP levels. Also, Jiang et al (2014) demonstrated that disruption of glutamate-glutamine homeostasis in hens treated with TOCP might also contribute to OPIDN. Finally, a study in China by Zou et al (2012) concludes that TOCP exposure causes changes in the autophagy-related proteins Atg1, Atg5, and Becln1 and these changes may contribute to OPIDN.…”

Emergencies and Critical Care of Commonly Kept Fowl

“…86 Other intoxications are common in fowl, such as coccidiostats in waterfowl (found in chicken-formulated commercial diets) or pesticides (dimetridazole and organophosphorus pesticides). 87,88…”