Tags

Type your tag names separated by a space and hit enter

Phenidone protects the nigral dopaminergic neurons from LPS-induced neurotoxicity.
Neurosci Lett. 2008 Nov 07; 445(1):1-6.NL

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+Show Affiliations

Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18760329

Citation

Li, Zhengyi, et al. "Phenidone Protects the Nigral Dopaminergic Neurons From LPS-induced Neurotoxicity." Neuroscience Letters, vol. 445, no. 1, 2008, pp. 1-6.
Li Z, Choi DY, Shin EJ, et al. Phenidone protects the nigral dopaminergic neurons from LPS-induced neurotoxicity. Neurosci Lett. 2008;445(1):1-6.
Li, Z., Choi, D. Y., Shin, E. J., Hunter, R. L., Jin, C. H., Wie, M. B., Kim, M. S., Park, S. J., Bing, G., & Kim, H. C. (2008). Phenidone protects the nigral dopaminergic neurons from LPS-induced neurotoxicity. Neuroscience Letters, 445(1), 1-6. https://doi.org/10.1016/j.neulet.2008.08.053
Li Z, et al. Phenidone Protects the Nigral Dopaminergic Neurons From LPS-induced Neurotoxicity. Neurosci Lett. 2008 Nov 7;445(1):1-6. PubMed PMID: 18760329.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phenidone protects the nigral dopaminergic neurons from LPS-induced neurotoxicity. AU - Li,Zhengyi, AU - Choi,Dong-Young, AU - Shin,Eun-Joo, AU - Hunter,Randy L, AU - Jin,Chun Hui, AU - Wie,Myung-Bok, AU - Kim,Min Soo, AU - Park,Seok Joo, AU - Bing,Guoying, AU - Kim,Hyoung-Chun, Y1 - 2008/08/22/ PY - 2008/06/10/received PY - 2008/08/12/revised PY - 2008/08/18/accepted PY - 2008/9/2/pubmed PY - 2009/4/15/medline PY - 2008/9/2/entrez SP - 1 EP - 6 JF - Neuroscience letters JO - Neurosci Lett VL - 445 IS - 1 N2 - 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. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/18760329/Phenidone_protects_the_nigral_dopaminergic_neurons_from_LPS_induced_neurotoxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(08)01168-3 DB - PRIME DP - Unbound Medicine ER -