Inhibition of poly (ADP-ribose) synthetase prevents the neurological development of experimental allergic encephalomyelitis

G. S. Scott, P. Hake, A. L. Salzman, Csaba Szabo

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Experimental allergic encephalomyelitis (EAE) is a cell-mediated autoimmune disease of the central nervous system (CNS) which has been well characterized as an animal model of multiple sclerosis. Although the precise mechanisms involved in the etiology of both disorders remains undefined, recent evidence has demonstrated a role for peroxynitrite in disease development. As our group has previously shown that peroxynitrite mediates cytotoxicity via the activation of poly (ADP-ribose) synthetase (PARS), we have examined the effect of PARS inhibitors on the progression of EAE. Male Lewis rats (200-250g) inoculated for EAE were either orally dosed with 5-iodo-6-amino-1,2-benzopyrone (BP, 200 mg/kg body weight) or treated i.p. with 3-aminobenzamide (3AB, 30 mg/kg body weight) once daily from days 7 to 11 post-inoculation. Animals were then monitored for neurological disease signs. Administration of 3AB delayed the course of the disease. Administration of BP induced a marked suppression of the neurological development of EAE. The drug-treated animals demonstrated both a delay in the onset as well as a reduction in the incidence and severity of disease signs. In conclusion, the results of the present study indicate an involvement of PARS activation in the pathogenesis of EAE. However, further work is required to fully elucidate the precise role of PARS in disease etiology.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998
Externally publishedYes

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Poly Adenosine Diphosphate Ribose
NAD ADP-ribosyltransferase
neurodevelopment
Autoimmune Experimental Encephalomyelitis
Ligases
encephalitis
Peroxynitrous Acid
Animals
etiology
Autoimmune Diseases of the Nervous System
Body Weight
Chemical activation
body weight
autoimmune diseases
sclerosis
disease course
disease incidence
disease severity
Multiple Sclerosis
Neurology

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Inhibition of poly (ADP-ribose) synthetase prevents the neurological development of experimental allergic encephalomyelitis. / Scott, G. S.; Hake, P.; Salzman, A. L.; Szabo, Csaba.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

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