Phenidone, a dual inhibitor of cyclooxygenases and lipoxygenases, ameliorates rat paralysis in experimental autoimmune encephalomyelitis by suppressing its target enzymes

• Published in: Brain research 2005-02, Vol.1035 (2), p.206-210
• Main Authors: Moon, Changjong, Ahn, Meejung, Wie, Myung-Bok, Kim, Hyung-Min, Koh, Chang-Sung, Hong, Seong-Chul, Kim, Moon-Doo, Tanuma, Naoyuki, Matsumoto, Yoh, Shin, Taekyun
• Format: Article
• Language: English
• Subjects: 5-Lipoxygenase; Animals; Arachidonate 5-Lipoxygenase - biosynthesis; COX-2; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - therapeutic use; Cyclooxygenase(COX)-1; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - enzymology; Experimental autoimmune encephalomyelitis; Lipoxygenase Inhibitors - therapeutic use; Male; Membrane Proteins; Paralysis - drug therapy; Paralysis - enzymology; Phenidone; Prostaglandin-Endoperoxide Synthases - biosynthesis; Pyrazoles - therapeutic use; Rats; Rats, Inbred Lew
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2004.12.017

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.