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

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.