Protective effect of quinacrine on striatal dopamine levels in 6-OHDA and MPTP models of Parkinsonism in rodents

Recent studies provide evidence that phospholipase A(2) (PLA(2)) 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 PLA(2) 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, mate Wistar rats were infused with 6-OHDA (60 mug) 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 degreesC. 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 PLA(2) in MPTP and 6-OHDA induced neurotoxicity and oxidative stress. However, further studies are warranted to explore the therapeutic potential of PLA, inhibitors for the treatment of Parkinson's disease. (C) 2001 Elsevier Science Inc.