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.
Key wordscell culture chlorpyrifos hippocampal neurons neurotoxicity oxidative stress Trolox
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- 1.Yu. T. Salyha, “Potential neurotoxicity of chlorpyrifos and methods of its investigation,” Med. Chem., 11, No. 4, 69-72 (2009).Google Scholar
- 2.Yu. Salyha, “Biological effects assessment of chlorpyrifos and some aspects of its neurotoxicity,” Visn. Lviv Univ. Biol. Ser., 54, 3-14 (2010).Google Scholar
- 5.J. Flaskos, “The developmental neurotoxicity of organophosphorus insecticides: A direct role for the oxon metabolites,” Toxicol. Lett., No. 209, 86-93 (2012).Google Scholar
- 8.K. D. Whitney, F. J. Seidler, and T. A. Slotkin. “Developmental neurotoxicity of chlorpyrifos: cellular mechanisms,” Toxicol. Appl. Pharmacol., No. 134, 53–62 (1995).Google Scholar
- 9.A. Caughlan, K. Newhouse, U. Namgung, et al., “Chlorpyrifos induces apoptosis in rat cortical neurons that is regulated by a balance between p38 and ERK/JNK MAP kinases,” Toxicol. Sci., No.78, 125-134 (2004).Google Scholar
- 11.M. D. Saulsbury, S.O. Heyliger, K. Wang, et al., “Chlorpyrifos induces oxidative stress in oligodendrocyte progenitor cells,” Toxicol., No. 259, 1-9 (2009).Google Scholar
- 13.T. A. Slotkin and F. J. Seidler, “Comparative developmental neurotoxicity of organophosphates in vivo: transcriptional responses of pathways for brain cell development, cell signaling, cytotoxicity and neurotransmitter systems,” Brain Res. Bull., 72, No. 4/6, 232-274 (2007).PubMedCrossRefGoogle Scholar
- 14.S. Gandhi and A. Y. Abramov, “Mechanism of oxidative stress in neurodegeneration,” Oxidat. Med. Cell. Longevity., 2012, Article ID 428010, 11 pages, (2012).Google Scholar
- 15.K. Facecchia, L. A. Fochesato, S. D. Ray, et al., “Oxidative toxicity in neurodegenerative diseases: role of mitochondrial dysfunction and therapeutic strategies,” J. Toxicol., 2011, Article ID 683728, 12 pages, (2011).Google Scholar
- 17.J. T. Coyle and P. Puttfarcken, “Oxidative stress, glutamate, and neurodegenerative disorders,” Science, No. 262, 689-695 (1993).Google Scholar
- 18.M. Dumont, M. T. Lin, and M. F. Beal, “Mitochondria and antioxidant targeted therapeutic strategies for Alzheimer’s disease,” J. Alzheimer’s Dis., 20, No. 2, S633–S643 (2010).Google Scholar
- 24.Yu. Salyha, V. Rosalovsky, and R. Fedyakov “Glutathione system in erythrocytes of rats intoxicated by chlorpyrifos,” Visn. Lviv Univ. Biol. Ser., No. 60. 99-104, (2012).Google Scholar