Mediation of mitochondrial intrinsic pathways on the molecular mechanism of apoptosis by paraquat.

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

Florencia

Congreso; 2011 IBRO World Congress; 2011

International Brain Research Organization

Paraquat is able to generate oxidative stress producing brain damage after chronic exposure. The aim of this work was to evaluate the cortical and striatal mitochondrial production of superoxide anion in an experimental model of neurotoxicity induced by paraquat. Also, we investigated the possible mediation of the mitochondrial intrinsic pathways in the molecular mechanism of 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, superoxide dismutase (SOD) activity and aconitase/fumarase activity were measured. Also, Bax associated to the outer mitochondrial membrane was evaluated by Western Blot. Oxygen consumption was evaluated as parameter of mitochondrial function. Paraquat treatment increased O2.- levels by 22 and 17 % in cortical and striatal mitochondria, respectively. Evaluation of SOD activity by cortical and striatal mitochondria showed significant increases of 63 and 68 % 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 and decreased oxygen consumption in mitochondria from both brain areas. The results show that paraquat treatment increases mitochondrial superoxide anion and causes mitochondrial dysfunction. The impairment of mitochondrial function and the presence of Bax in this organelle suggest the involvement of mitochondria in the mechanism of apoptosis induced by paraquat.