Ethoprophos induces rats' brain injury and neurobehavioral impairment via transcriptional activation of glial fibrillary acidic protein and tubulin-associated unit even at the threshold inhibition of acetylcholinesterase: A 90-days study

摘要

Ethoprophos, a common organophosphate nematicide, has adverse effects on the nervous system. However, the specific mechanism of its neurotoxicity is unclear. Here, we have studied the possible involvement of brain glial fibrillary acidic protein and tubulin-associated unit in the neurotoxicity mechanism of ethoprophos, even at the threshold inhibition of acetylcholinesterase. The adult male rats were divided into four groups (n = 8/group), including the control and exposed groups that were orally received ethoprophos at the low (0.56 mg/kg), median (1.12 mg/kg), and high doses (2.24 mg/kg) for 90 days. Sub-chronic exposure to ethoprophos exhibited a significant decline in the brain activity and mRNA gene expression of acetylcholinesterase, while the levels of dopamine and serotonin were markedly increased at the medium and high doses (p ＜ 0.01). Ethoprophos increased the anxiety-like behavior in rats subjected to the open field quiz and induced many histopathological alterations in the brain. Furthermore, ethoprophos markedly (p ＜ 0.05) increased malondialdehyde and nitric oxide levels, while the glutathione content, together with the activities of glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, and catalase were decreased in a dose-dependent manner. Additionally, there was a dose-dependent up-regulation in the mRNA gene expression of brain glial fibrillary acidic protein and tubulin-associated unit in the ethoprophos-exposed rats (p ＜ 0.05). The obtained data deliver the initial demonstration about the involvement of this up-regulation in the neurotoxicity mechanism of ethoprophos and may use as a biomarker for organophosphate-induced neurodegeneration.