Acute L: -DOPA effect on hydroxyl radical- and DOPAC-levels in striatal microdialysates of parkinsonian rats.
The object of the current study was to determine the effect of L: -3,4-dihydroxyphenylalanine (L: -DOPA) on the in vivo striatal microdialysate levels of the respective dopamine and serotonin metabolites 3,4-dihydroxyphenlalanine (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) and hydroxyl radical level (HO(*); 2,3- and 2,5-dihydroxybenzoic acid, 2,3- and 2,5-DHBA) in adult rats made parkinsonian by treatment at 3 days after birth with the neurotoxin 6-hydroxydopamine (6-OHDA; 66.7 microg, base form, on each side; desipramine pretreatment, 1 h). Using HPLC/ED we found that in 6-OHDA-lesioned rats the basal striatal extraneuronal level of DOPAC was dramatically reduced and constituted only approximately 4.5% of referenced value (intact rats). Conversely, the striatal microdialysate level of 5-HIAA was elevated 2-fold in 6-OHDA-lesioned rats. Acute L: -DOPA (60 mg/kg i.p.; S-carbidopa pretreatment, 12.5 mg/kg i.p., 30 min) produced a rapid rise in the extraneuronal DOPAC in both tested groups but to a much greater extent in intact rats (P < 0.05). Levels of HO(*) (spin-trap products of salicylate, 2,3- and 2,5-DHBA) were elevated 2-fold in 6-OHDA-lesioned rats. However, L: -DOPA did not enhance HO(*) production; acute 6-OHDOPA treatment (60 mg/kg i.p.) also did not alter HO(*) production. In summary, L: -DOPA, an effective drug in ameliorating PD symptoms, did not acutely pose a risk for HO(*) generation in parkinsonian rats. We conclude that L: -DOPA is not likely to generate reactive oxygen species in humans nor is L: -DOPA likely to accelerate PD in humans.
Nowak
Przemysław
P
Department of Pharmacology, Medical University of Silesia, 41-808, Zabrze, Poland.
Kostrzewa
Rose Anna
RA
Skaba
Dariusz
D
Kostrzewa
Richard M
RM
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003342:Corpus Striatum / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D007276:Injections, Intraventricular; D007980:Levodopa / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D017551:Microdialysis / Q000379:methods; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D011247:Pregnancy; D051381:Rats; D013565:Sympatholytics / Q000633:toxicity; D013997:Time Factors
D000978:Antiparkinson Agents; D013565:Sympatholytics; D015102:3,4-Dihydroxyphenylacetic Acid; D017665:Hydroxyl Radical; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D016627:Oxidopamine