Increased reactive oxygen species production in the brain after repeated low-dose pesticide paraquat exposure in rats. A comparison with peripheral tissues.
The pesticide paraquat (PQ) was found to be a suitable xenobiotic to model Parkinson's disease. The reactive oxygen species (ROS) production was suggested to be the main cause of PQ toxicity but very few evidences were found for its generation in the brain in vivo after ip administration. We compared the effects of PQ-induced ROS generation between the brain structures and the peripheral tissues using two different hydroxyl radical generation markers. Repeated but not single ip PQ administration increased the levels of ROS in the striatal homogenates but, when measured in the extracellular microdialysis filtrate, no change was observed. The increased dopamine release was detected in the striatum after the fourth PQ administration and its basal levels were decreased. A single treatment with the pesticide did not influence ROS production in the lungs or kidneys but repeated intoxication decreased its levels. These results suggest that repeated, systemic administration of a low dose of PQ triggers intracellular ROS formation in the brain and can cause slowly progressing degenerative processes, without the toxic effects in the peripheral tissues.
Kuter
Katarzyna
K
Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland. kuter@if-pan.krakow.pl
Nowak
Przemysław
P
Gołembiowska
Krystyna
K
Ossowska
Krystyna
K
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002396:Catechols / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005841:Gentisates / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D062385:Hydroxybenzoates; D008297:Male; D017551:Microdialysis; D009928:Organ Specificity; D010226:Parabens / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020156:Salicylic Acid / Q000378:metabolism
D002396:Catechols; D005841:Gentisates; D006540:Herbicides; D062385:Hydroxybenzoates; D010226:Parabens; D017382:Reactive Oxygen Species; C009135:2,3-dihydroxybenzoic acid; C038193:4-hydroxybenzoic acid; D020156:Salicylic Acid; D010269:Paraquat; C010925:2,5-dihydroxybenzoic acid; D004298:Dopamine