Chlorpyrifos Leads to Oxidative Stress-Induced Death of Hippocampal Cells in Vitro

Chlorpyrifos (ClPF) is a broad-spectrum organophosphate insecticide widely used in agriculture, industry, and at home. Like all organophosphates, ClPH affects the nervous system by inhibiting the enzyme acetylcholinesterase (AChE). In addition, it is transformed in higher animals into ClPF-oxon that is about 3000 times more potent against the nervous system than ClPF itself. As was found recently, the action on ACh is not the only mechanism of ClPF toxicity. One other mechanism of this organophosphate is induction of oxidative stress leading to generation of free radicals. We investigated the effects of ClPF on hippocampal cells of the rat in vitro and focused our attention on mediation of its cytotoxic effect related to the production of reactive oxygen species. Transfection of cultured hippocampal cells by green fluorescent protein (GFP) was used. We studied the dose dependence of the intensity of ClPF-induced damage and cell death of hippocampal neurons in vitro and the dependence on the duration of ClPF action. We also observed survival of the cells incubated in the media with only ClPF and under the same conditions but with the addition of Trolox as an antioxidant. It was found that Trolox demonstrated clear neuroprotective effects at all concentrations of ClPF tested during the research period. It is concluded that the negative effect of ClPF on hippocampal neurons results, to a considerable extent, in the development of oxidative stress.