Role of nitric oxide in rotenone-induced nigro-striatal injury.
Rotenone, a widely used pesticide, causes a syndrome in rats that mimics, both behaviorally and pathologically, the symptoms of Parkinson's disease. The present study evaluated the role of nitric oxide in rotenone-induced nigro-striatal injury. After administration of rotenone in rats for 40 days, there was a moderate but significant injury of the nigro-striatal pathway indicated by a 47% decrease in striatal dopamine levels and a 28% loss of substantia nigra tyrosine hydroxylase-immunopositive neurons. Furthermore, a significant (37%) increase in the number of cells positive for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) in the striatum was observed, accompanied by a 83% increase in nitric oxide synthase (NOS) activity and a significant increase in the production of 3-nitrotyrosine (3-NT). There was a significant increase (45%) in the optical density of NADPH-d staining and an increase (72%) in NOS activity in the substantia nigra. Moreover, administration of the neuronal NOS inhibitor 7-nitroindazole significantly attenuated the increased NOS activity and 3-NT production, and provided significant protection against rotenone-induced nigro-striatal injury. Our data suggest that chronic rotenone administration can lead to significant injury to the nigro-striatal system, mediated by increased generation of nitric oxide.
He
Yi
Y
Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA.
Imam
Syed Z
SZ
Dong
Zaojun
Z
Jankovic
Joseph
J
Ali
Syed F
SF
Appel
Stanley H
SH
Le
Weidong
W
D000818:Animals; D001923:Brain Chemistry; D002452:Cell Count; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007191:Indazoles / Q000494:pharmacology; D007306:Insecticides / Q000633:toxicity; D009252:NADPH Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D030421:Peroxynitrous Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000032:analysis / Q000097:blood / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013995:Time; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis; D014475:Uncoupling Agents / Q000633:toxicity
D004791:Enzyme Inhibitors; D007191:Indazoles; D007306:Insecticides; D014475:Uncoupling Agents; D012402:Rotenone; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D014446:Tyrosine 3-Monooxygenase; D009252:NADPH Dehydrogenase; C080122:7-nitroindazole; D004298:Dopamine