a preliminary investigation into the impact of a pesticide combination on human neuronal and glial cell lines in vitro初步调查的影响农药组合对人类神经元和神经胶质细胞系体外.pdfVIP

A Preliminary Investigation into the Impact of a Pesticide Combination on Human Neuronal and Glial Cell Lines In Vitro 1 1 1 1 1 Michael D. Coleman *, John D. O’Neil , Elizabeth K. Woehrling , Oscar Bate Akide Ndunge , Eric J. Hill , Andre Menache2, Claude J. Reiss2 1 School of Life and Health Sciences, Aston University, Birmingham, United Kingdom, 2 Antidote Europe, Perpignan, France Abstract Many pesticides are used increasingly in combinations during crop protection and their stability ensures the presence of such combinations in foodstuffs. The effects of three fungicides, pyrimethanil, cyprodinil and fludioxonil, were investigated together and separately on U251 and SH-SY5Y cells, which can be representative of human CNS glial and neuronal cells respectively. Over 48h, all three agents showed significant reductions in cellular ATP, at concentrations that were more than tenfold lower than those which significantly impaired cellular viability. The effects on energy metabolism were reflected in their marked toxic effects on mitochondrial membrane potential. In addition, evidence of oxidative stress was seen in terms of a fall in cellular thiols coupled with increases in the expression of enzymes associated with reactive species formation, such as GSH peroxidase and superoxide dismutase. The glial cell line showed significant responsiveness to the toxin challenge in terms of changes in antioxidant gene expression, although the neuronal SH-SY5Y line exhibited greater vulnerability to toxicity, which was reflected in significant increases in caspase-3 expression, which is indicative of the initiation of apoptosis. Cyprodinil was the most toxic agent individually, although oxida