Fludioxonil, a phenylpyrrol pesticide, induces Cytoskeleton disruption, DNA damage and apoptosis via oxidative stress on rat glioma cells

Pesticides products are widely used to increase food productivity and to decrease food-borne diseases. Fludioxonil is a worldwide used phenylpyrrol fungicide. This pesticide can induce serious effects on human health especially on nervous system. We assessed the role of oxidative stress in the toxicity of Fludioxonil and examined its apoptotic mechanism of action on rat neural cells (F98). We have shown that the increasing concentration of Fludioxonil reduces the percentage of living F98 cells viability and increases the levels of reactive oxygen species and malondialdheydes. The reduction of cells proliferation was demonstrated with an accumulation in G2/M phase. The immunocytochemical analysis has shown that Fludioxonil induced the disruption of the cytoskeleton. DNA damage was also provoked in a concentration dependent manner as illustrated by the comet assay. The depolarization of the mitochondria and the positive Annexin V FITC-PI confirmed the apoptosis induced by this fungicide. Interestingly, the F98 cells viability and ROS levels were restored with N-acetylcysteine pre-treatment. These results highlight the involvement of oxidative stress in the toxicity induced by this fungicide, and that free radicals generation plays a key role in the induction of apoptosis probably induced via the mitochondrial pathway.