Paraquat tratment increases cortical and striatal mitocondrial reactive oxygen species.

CZERNICZYNIEC, A.; BUSTAMANTE, J.; LORES ARNAIZ, S.

Uspallata

Congreso; V Neurotoxicity Society Meeting; 2011

Neurotoxicity Society

Exposure to paraquat can cause significant brain damage due to its ability to generate oxidative stress. The aim of this work was to evaluate the cortical and striatal mitochondrial production of reactive oxygen species in an experimental model of neurotoxicity induced by paraquat. Also, we investigated the involvement of mitochondria in the mechanism of cell death by apoptosis. Sprague-Dawley adult female rats received paraquat (10 mg/Kg i.p.) or saline once a week during a month. Superoxide anion (O2.-) levels, hydrogen peroxide (H2O2) production, Complex I activity and aconitase/fumarase activity were measured. Also, Bax associated to the outer mitochondrial membrane was evaluated by Western Blot. Paraquat treatment decreased Complex I activity by 25 and 34 % and increased O2.- levels by 22 and 17 % in cortical and striatal mitochondria, respectively. Evaluation of H2O2 production by cortical and striatal mitochondria showed significant increases of 13 and 48 % respectively after paraquat treatment. Aconitase/fumarase activity ratios decreased by 52 and 53 % in cortical and striatal mitochondria after paraquat treatment, respectively. Also, paraquat treatment increased Bax expression in mitochondria from both brain areas. The above results show that systemic administration of paraquat during a month increases mitochondrial reactive oxygen species production and causes mitochondrial dysfunction. The impairment of mitochondrial function and the presence of Bax in this organelle suggest the mediation of the mitochondrial intrinsic pathways of the molecular mechanism of apoptosis induced by paraquat.