Protective effect of quinacrine on striatal dopamine levels in 6-OHDA and MPTP models of Parkinsonism in rodents.
Recent studies provide evidence that phospholipase A2 (PLA2) may play a role in the development of experimental parkinsonism. In this investigation an attempt was made to determine a possible protective effect of quinacrine (QNC), a PLA2 inhibitor on MPTP as well as 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rodents. For MPTP studies, adult male mice (C57 BL) were treated with MPTP (30 mg/kg, i.p.) daily for 5 days. QNC was injected i.p. in the doses of 0, 10, 30 and 60 mg/kg daily 30 min before MPTP in four different groups. Two other groups of mice received either vehicle (control) or a high dose of QNC (60 mg/kg). Two hours after the last injection of MPTP, striata were collected for the analysis of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and glutathione (GSH). For the 6-OHDA study, male Wistar rats were infused with 6-OHDA (60 microg) in the right striatum under chloral hydrate anesthesia. The rats in different groups were treated with 0, 5, 15 and 30 mg/kg QNC (i.p.) for 4 days, while first injection was given 30 min before 6-OHDA. On day 5, rats were sacrificed and striata were stored at -80 degrees C. Administration of MPTP or 6-OHDA significantly reduced striatal DA, which was significantly attenuated by QNC. Concomitant treatment with QNC also protected animals against MPTP or 6-OHDA-induced depletion of striatal GSH. Our findings clearly suggest the role of PLA2 in MPTP and 6-OHDA induced neurotoxicity and oxidative stress. However, further studies are warranted to explore the therapeutic potential of PLA2 inhibitors for the treatment of Parkinson's disease.
Tariq
M
M
Neuroscience Research Group, Armed Forces Hospital, Riyadh, Saudi Arabia.
Khan
H A
HA
Al Moutaery
K
K
Al Deeb
S
S
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013565:Sympatholytics
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D013565:Sympatholytics; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D010740:Phospholipases; D005978:Glutathione; D011796:Quinacrine; D004298:Dopamine; D006719:Homovanillic Acid