Phenidone, a dual inhibitor of cyclooxygenases and lipoxygenases, ameliorates rat paralysis in experimental autoimmune encephalomyelitis by suppressing its target enzymes.
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.
Moon
Changjong
C
Department of Veterinary Medicine, Aradong 1, Cheju National University, Jeju 690-756, South Korea.
Ahn
Meejung
M
Wie
Myung-Bok
MB
Kim
Hyung-Min
HM
Koh
Chang-Sung
CS
Hong
Seong-Chul
SC
Kim
Moon-Doo
MD
Tanuma
Naoyuki
N
Matsumoto
Yoh
Y
Shin
Taekyun
T
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000201:enzymology*; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins; D010243:Paralysis / Q000188:drug therapy* / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D011720:Pyrazoles; D001094:Arachidonate 5-Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; C015429:phenidone