The reduced glutathione and S-nitrosothiols levels in acute phase of experimental demyelination--pathophysiological approach and possible clinical relevancy.
Multiple sclerosis (MS) is characterized by inflammatory process associated with nitric oxide (NO) and the related species production in CNS, which can nitrosylate protein thiols and modulate their structure and functions, also reducing the CNS content of redox active compounds, such as glutathione (GSH). We have evaluated the relationships between S-nitrosothiols (RSNO) and GSH in the experimental model of MS - experimental autoimmune encephalomyelitis (EAE), during the treatment with inducible NO synthase inhibitor - aminoguanidine (AG) and thiol donor molecule - N-acetyl-L-cysteine (NAC).


METHODS
EAE was induced by myelin basic protein, dissolved in phosphate-buffered saline (PBS), emulsified in the complete Freund's adjuvant (CFA) followed by injections of Pertussis toxin. Animals assigned to the control (PBS), EAE, CFA, EAE+AG, AG, EAE+NAC and NAC groups were scored daily for the clinical signs of EAE. RSNO and GSH were evaluated in whole encephalitic mass and cerebellum.


RESULTS
RSNO concentration was increased in EAE-untreated animals compared to the AG and NAC-treated EAE animals (p<0.05). Also, during the treatment with AG and NAC, GSH concentration was increased compared to the untreated animals (p<0.05). The EAE clinical signs were reduced in EAE-treated animals compared to the other groups (p<0.05).


CONCLUSIONS
The findings of our work suggest a potential role of RSNO and GSH in early clinical presentation of experimental MS, that might be also useful as predictive parameters for MS treatment directed to increased GSH and thiol pool in CNS.
Clinic of Neurology, University Clinical Centre of Nis, Boulevard Dr Zorana Djindjica 48, 18000 Nis, Serbia. srljub@gmail.com
S
S
Ljubisavljevic
I
I
Stojanovic
R
R
Pavlovic
S
S
Stojnev
I
I
Stevanovic
D
D
Sokolovic
D
D
Pavlovic
D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D007150:Immunohistochemistry; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026403:S-Nitrosothiols / Q000378:metabolism*
D015415:Biomarkers; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D005978:Glutathione