title: Phenidone protects the nigral dopaminergic neurons from LPS-induced neurotoxicity.
abstract: Anti-inflammatory drugs such as ibuprofen appear to prevent the development of Parkinson's disease (PD); however, long-term use has undesirable side-effects. A new strategy for anti-inflammatory drug therapy is using a dual inhibitor of COX and lipooxygenase (LOX). Here, we compared the dopaminergic neuroprotective property of phenidone (a dual COX and LOX inhibitor) with COX or LOX inhibitors including SC-560 (a COX-1 inhibitor), aspirin (a COX-1/2 inhibitor), meloxicam (a preferential COX-2 inhibitor), caffeic acid (a 5-LOX inhibitor), and esculetin (a 5, 12-LOX inhibitor) in our lipopolysaccharide (LPS)-induced PD animal model. Our results show that COX-2 and 5-LOX play a major role in LPS-induced dopaminergic neurotoxicity, as meloxicam and phenidone attenuated LPS-induced oxidative stress and meloxicam, phenidone, and caffeic acid attenuated dopaminergic neurodegeneration, while SC-560, aspirin, and esculetin did not. In addition, phenidone was superior in attenuating LPS-induced dopaminergic neurodegeneration and microglia activation, probably as a result of dual inhibition of COX-2 and LOX. Therefore, dual inhibition of COX and LOX with phenidone represents a promising new candidate for anti-inflammatory drug therapy, and may provide a novel therapeutic approach for inflammation-related neurodegenerative diseases including PD.
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.
authors.forename: Zhengyi
authors.initials: Z
authors.lastname: Li
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Choi
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Shin
authors.forename: Randy L
authors.initials: RL
authors.lastname: Hunter
authors.forename: Chun Hui
authors.initials: CH
authors.lastname: Jin
authors.forename: Myung-Bok
authors.initials: MB
authors.lastname: Wie
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Kim
authors.forename: Seok Joo
authors.initials: SJ
authors.lastname: Park
authors.forename: Guoying
authors.initials: G
authors.lastname: Bing
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim