Paraquat induces alternation of the dopamine catabolic pathways and glutathione levels in the substantia nigra of mice

• Published in: Toxicology letters Vol. 188; no. 2; pp. 148 - 152
• Main Authors: Kang, Min Jeong, Gil, Suk Ju, Koh, Hyun Chul
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 24.07.2009; Elsevier
• Subjects: 3,4-Dihydroxyphenylacetic acid; 3-Methoxytyramine; Animals; Biological and medical sciences; Dopamine; Dopamine - metabolism; Glutathione; Glutathione Disulfide - metabolism; Herbicides - toxicity; Homovanillic acid; Immunohistochemistry; Male; Medical sciences; Mice; Mice, Inbred C57BL; Neurons - drug effects; Neurons - enzymology; Neurons - metabolism; Paraquat; Paraquat - toxicity; Parkinson Disease - etiology; Pesticides, fertilizers and other agrochemicals toxicology; Substantia Nigra - drug effects; Substantia Nigra - enzymology; Substantia Nigra - metabolism; Toxicology; Tyrosine 3-Monooxygenase - metabolism; 3-Methoxytyramine; Paraquat; Dopamine; 3,4-Dihydroxyphenylacetic acid; Homovanillic acid; Glutathione; Pesticides; Rodentia; Central nervous system; 3.4-Dihydroxyphenylacetic acid; Catecholamine; Herbicide; Encephalon; Quaternary ammonium compound; Vertebrata; Mammalia; Locus niger; Mouse; Aminoacid; Animal; Neurotransmitter
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2009.03.026

The herbicide paraquat (PQ) is a strong redox agent that participates in the formation of reactive oxygen species (ROS) and induces toxicity in the nigrostriatal dopaminergic system. In this study, we investigated the effect of PQ on dopamine (DA) and glutathione levels in the substantia nigra (SN) of mice. Male C57BL/6 mice (aged 7 weeks and 23–25 g) were used for this study. The mice were treated with normal saline (vehicle) and PQ (10 mg/kg, i.p.) twice weekly for three consecutive weeks. We measured changes in tyrosine hydroxylase (TH) immunoreactivity, DA and its metabolites, and glutathione (reduced and oxidized) in the SN. After repeated PQ administration, the density of TH-positive neurons in the substantia nigra pars compacta (SNpc) decreased as compared to the control. Levels of DA and homovanillic acid (HVA) decreased significantly in the PQ-treated mice ( p < 0.05), but levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) did not change. The rate of DA oxidation increased significantly in the SNpc, whereas the O-methylation pathway remained unchanged. Levels of reduced glutathione (GSH) in the SNpc decreased more in the PQ group than in the control group, while levels of oxidized glutathione (GSSG) increased in same region. We propose that repeated PQ injection induces dopaminergic neurotoxicity through generation of oxidative stress, and that this toxicity is related to the decline of GSH in the SNpc. The neurotoxic mechanism may specifically involve enhancement of the oxidative pathway of DA metabolism through coupling with the antioxidant GSH system of the SN.