Impairment of striatal mitochondrial function by acute paraquat poisoning.
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 h. 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. As a consequence, mitochondrial dysfunction could probably lead to alterations in cellular bioenergetics.
Instituto de Bioquímica y Medicina Molecular (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina. aczerni@ffyb.uba.ar.
Analía
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Czerniczyniec
Instituto de Bioquímica y Medicina Molecular (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina.
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Lanza
Instituto de Bioquímica y Medicina Molecular (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina.
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Karadayian
Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Facultad de Medicina, Universidad Abierta Interamericana, Buenos Aires, Argentina.
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Bustamante
Instituto de Bioquímica y Medicina Molecular (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina.
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Lores-Arnaiz
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D010101:Oxygen Consumption / Q000187:drug effects*; D010269:Paraquat / Q000506:poisoning*; D051381:Rats; D017207:Rats, Sprague-Dawley
D045222:Electron Transport Chain Complex Proteins; D006861:Hydrogen Peroxide; D010269:Paraquat
Acute paraquat; Membrane potential; Mitochondrial function; Oxygen consumption