Phenidone protects the nigral dopaminergic neurons from LPS-induced neurotoxicity.
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| 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.
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| Authors | Zhengyi Li, Dong-Young Choi, Eun-Joo Shin, Randy L Hunter, Chun Hui Jin, Myung-Bok Wie, Min Soo Kim, Seok Joo Park, Guoying Bing, Hyoung-Chun Kim |
| Journal | Neuroscience letters (Neurosci Lett) Vol. 445 Issue 1 Pg. 1-6 (Nov 07 2008) ISSN: 0304-3940 [Print] Ireland |
| PMID | 18760329 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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