Differential effects of chronic L-dopa treatment on lipid peroxidation in the mouse brain with or without pretreatment with 6-hydroxydopamine.
Whether or not chronic L-dopa treatment (100 mg/kg, intraperitoneally (i.p.), twice daily for 4 weeks) alters lipid peroxidation in the brain as an indicator of neuronal damage was examined in normal mice and mice in which catecholamine (CA) neurons had been injured previously by the administration of 6-hydroxydopamine (6-OHDA), followed by recovery. In normal mice, chronic L-dopa treatment reduced the thiobarbituric acid reacting substances (TBARS) level, an indicator of lipid peroxidation, in the cerebral cortex. In contrast, in mice with CA neuronal injury induced by pretreatment with 6-OHDA, the chronic L-dopa treatment markedly increased the TBARS in the striatum and frontal cortex, despite recovery of the striatal dopamine levels similar to those in the control mice. These findings suggest that the long-term high-dose administration of L-dopa enhances the progression of neuronal damage in patients with injured CA neurons such as those with Parkinson's disease.
Ogawa
N
N
Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical School, Japan.
Asanuma
M
M
Kondo
Y
Y
Kawada
Y
Y
Yamamoto
M
M
Mori
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002395:Catecholamines / Q000502:physiology; D006719:Homovanillic Acid / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D002395:Catecholamines; D009419:Nerve Tissue Proteins; D017392:Thiobarbituric Acid Reactive Substances; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D016627:Oxidopamine; D006719:Homovanillic Acid