Chronic administration of rotenone increases levels of nitric oxide and lipid peroxidation products in rat brain.
The complex I inhibitor rotenone is a neurotoxin that has been proposed to induce Parkinson-like degeneration. As the mechanisms of rotenone toxicity are not fully understood, the present study addresses the question of whether rotenone induces NO production and lipid peroxidation-like products, that is, thiobarbituric acid reactive substances (TBARS). Rotenone at a dose of 1.5 mg kg(-1) i.p. was administered to rats daily for 10, 20, 30, and 60 days, and NO and TBARS were measured in the frontal cortex and in the striatum. On the 1st and 10th day, there were no increases in NO and TBARS levels, after 20 days, the NO and TBARS levels were increased in the striatum. After 30 and 60 days, NO and TBARS levels were increased in striatum and frontal cortex. Behaviorally, on days 30 and 60, the rats exhibited akinesia and rigidity in the catalepsy test. These results show that chronic administration of rotenone over a long period is capable of increasing NO and TBARS in the cortex and striatum and mimics Parkinson's disease (PD)-like behavioral symptoms that are akinesia and rigidity in rats.
Bashkatova
Valentina
V
Institute of Pharmacology, Russian Academy of Medical Sciences, 125315, Russia.
Alam
Mesbah
M
Vanin
Anatoly
A
Schmidt
Werner J
WJ
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012402:Rotenone / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013997:Time Factors; D014475:Uncoupling Agents / Q000494:pharmacology*
D017392:Thiobarbituric Acid Reactive Substances; D014475:Uncoupling Agents; D012402:Rotenone; D009569:Nitric Oxide