Impairment of striatal mitochondrial function by acute paraquat poisoning.

CZERNICZYNIEC, A; LANZA, ESTELA M; BUSTAMANTE, J.; LORES ARNAIZ, S

JOURNAL OF BIOENERGETICS AND BIOMEMBRANES

SPRINGER/PLENUM PUBLISHERS

Lugar: New York; Año: 2015 vol. 47 p. 395 - 408

0145-479X

Mitochondria are essential for survival. Their primary function is to support aerobic respiration and to provide energy for intracellular metabolic pathways. Paraquat is a redox cycling agent capable of generating reactive oxygen species. The aim of the present study was to evaluate changes in cortical and striatal mitochondrial function in an experimental model of acute paraquat toxicity and to compare if the brain areas and the molecular mechanisms involved were similar to those observed after chronic exposure. Sprague-Dawley rats received paraquat (25 mg/Kg i.p.) or saline and were sacrificed after 24 hours. Paraquat treatment decreased complex I and IV activity by 37 and 21 % respectively in striatal mitochondria. Paraquat inhibited striatal state 4 and state 3 KCN-sensitive respiration by 80% and 62% respectively, indicating a direct effect on respiratory chain. An increase of 2.2 fold in state 4 and 2.3 fold in state 3 in KCN-insensitive respiration was observed in striatal mitochondria from paraquat animals, suggesting that paraquat redox cycling also consumed oxygen. Paraquat treatment increased hydrogen peroxide production (150%), TBARS production (42%) and cardiolipin oxidation/depletion (12%) in striatal mitochondria. Also, changes in mitochondrial polarization was induced after paraquat treatment. However, no changes were observed in any of these parameters in cortical mitochondria from paraquat treated-animals.These results suggest that paraquat treatment induced a clear striatal mitochondrial dysfunction due to both paraquat redox cycling reactions and impairment of the mitochondrial electron transport, causing oxidative damage to lipids. As a consequence, mitochondrial dysfunction could probably lead to alterations in cellular bioenergetics.