L-arginine modifies free radical production and the development of experimental allergic encephalomyelitis.
OBJECTIVE
The present investigation examines the effects of increasing central nervous system (CNS) levels of nitric oxide (NO), via the administration of L-arginine, on the development of experimental allergic encephalomyelitis (EAE).


METHODS
EAE was induced in male Lewis rats (200-250 g).


METHODS
Normal rats were orally dosed with L-arginine (300 mg/kg body weight) once daily for 12 days. EAE-sensitised animals received L-arginine (300 mg/kg body weight) once daily from day 1 to 12 post-inoculation.


METHODS
Neurological and histological development of EAE were assessed. In addition, CNS cytosol levels of nitrite, superoxide and hydrogen peroxide were measured. Results were analysed using the Mann Whitney U-test and Chi-squared test.


RESULTS
L-arginine administration significantly delayed disease onset (p < 0.05) and reduced the severity of neurological (p < 0.05) and histological (p < 0.001) signs of EAE. Treatment with L-arginine caused a significant elevation in CNS nitrite concentrations (p < 0.05) which in EAE-sensitised animals was associated with a concomitant and dramatic decrease in superoxide (p < 0.05) and hydrogen peroxide (p < 0.05) levels.


CONCLUSIONS
The results suggest that NO may act as a protective molecule during the development of EAE possibly via the modulation of oxidant-mediated neuroinflammation.
Scott
G S
GS
William Harvey Research Institute, Charterhouse Square, University of London, UK.
Bolton
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D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005609:Free Radicals / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D013481:Superoxides; D009569:Nitric Oxide; D001120:Arginine; D006861:Hydrogen Peroxide