Mitochondrial susceptibility in a model of paraquat neurotoxicity.

CZERNICYNIEC, A.; LORES-ARNAIZ, S.; BUSTAMANTE J.

FREE RADICAL RESEARCH

TAYLOR & FRANCIS LTD

Lugar: Londres; Año: 2013 vol. 47 p. 614 - 623

1071-5762

Paraquat is a highly toxic herbicide capable of generating oxidative stress andproducing brain damage after chronic exposure. The aim of this research was to investigatethe contribution of mitochondria to the molecular mechanism of apoptosis in an in vivoexperimental model of paraquat neurotoxicity. Sprague-Dawley adult female rats receivedparaquat (10 mg/kg i.p.) or saline once a week during a month. Paraquat treatmentincreased cortical and striatal superoxide anion levels by 45% and 18%, respectively. As aconsequence, mitochondrial aconitase activity was significantly inhibited in cerebral cortexand striatum. Paraquat treatment increased cortical and striatal lipid peroxidation levels by16% and 28% respectively, as compared with control mitochondria Also, cortical andstriatal cardiolipin levels were decreased by 13% and 49%, respectively. Increased Bax andBak association to mitochondrial membranes was observed after paraquat treatment incerebral cortex and striatum. Also, paraquat induced cytochrome c and AIF release frommitochondria.These findings support the conclusion that a weekly dose of paraquat during fourweeks induces oxidative damage that activates mitochondrial pathways associated withmolecular mechanisms of cell death. The release of apoptogenic proteins frommitochondria to cytosol after paraquat treatment would be the consequence of an alterationin mitochondrial membrane permeability due to the presence of high superoxide anionlevels. Also, our results suggest that under chronic exposure, striatal mitochondria weremore sensitive to paraquat oxidative damage than cortical mitochondria. Even in thepresence of a high oxidative stress in striatum, equal levels of apoptosis were attained inboth brain areas.