Abstract
This study examined whether phenidone, a dual inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX), affects the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in the rat, and the expression of both COX-1/-2 and 5-LOX in EAE spinal cords. Oral phenidone (200 mg/kg) significantly suppressed the incidence and clinical severity of EAE paralysis. Western blot analysis showed that phenidone significantly inhibited the increases in COX-1/-2 and 5-LOX in the spinal cords of rats with EAE. This finding was paralleled by immunohistochemical observations. Overall, these findings suggest that COX-1/-2 and 5-LOX are important inflammatory mediators in the pathogenesis of EAE, and that the inhibition of both COX and LOX ameliorates the autoimmune disorder of the central nervous system.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arachidonate 5-Lipoxygenase / biosynthesis
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Cyclooxygenase 1
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / therapeutic use*
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Encephalomyelitis, Autoimmune, Experimental / drug therapy*
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Encephalomyelitis, Autoimmune, Experimental / enzymology*
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Lipoxygenase Inhibitors / therapeutic use*
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Male
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Membrane Proteins
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Paralysis / drug therapy*
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Paralysis / enzymology*
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Prostaglandin-Endoperoxide Synthases / biosynthesis
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Pyrazoles / therapeutic use*
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Rats
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Rats, Inbred Lew
Substances
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Lipoxygenase Inhibitors
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Membrane Proteins
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Pyrazoles
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Arachidonate 5-Lipoxygenase
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Cyclooxygenase 1
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases
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Ptgs1 protein, rat
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phenidone