Phenidone protects the nigral dopaminergic neurons from LPS-induced neurotoxicity.
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.
Li
Zhengyi
Z
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.
Choi
Dong-Young
DY
Shin
Eun-Joo
EJ
Hunter
Randy L
RL
Jin
Chun Hui
CH
Wie
Myung-Bok
MB
Kim
Min Soo
MS
Park
Seok Joo
SJ
Bing
Guoying
G
Kim
Hyoung-Chun
HC