title: Aminoguanidine and N-acetyl-cysteine supress oxidative and nitrosative stress in EAE rat brains.
abstract: Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of human multiple sclerosis (MS). We have evaluated the role of oxidative and nitrosative stress, as the causal factors in the development of EAE, responsible for the damage of cardinal cellular components, such as lipids, proteins and nucleic acids, resulting in demyelination, axonal damage, and neuronal death. EAE was induced in female Sprague-Dawley rats, 3 months old (300±20 g), by immunization with myelin basic protein in combination with Complete Freund's adjuvant (CFA). The animals were divided into seven groups: control, EAE, CFA, EAE+aminoguanidine (AG), AG, EAE+N-acetyl-L-cysteine (NAC) and NAC. The animals were sacrificed 15 days after EAE induction, and the levels of nitrosative and oxidative stress were determined in 10% homogenate of the whole encephalitic mass. In EAE rats, brain NO production and MDA level were significantly increased (P<0.001) compared to the control values, whereas AG and NAC treatment decreased both parameters in EAE rats compared to EAE group (P<0.001). Glutathione (GSH) was reduced (P<0.001) in EAE rats in comparison with the control and CFA groups, but increased in EAE+AG and EAE+NAC group compared to the EAE group (P<0.01). Superoxide dismutase (SOD) activity was significantly decreased (P<0.001) in the EAE group compared to all other experimental groups. The clinical expression of EAE was significantly decreased (P<0.05) in the EAE groups treated with AG and NAC compared to EAE rats, during disease development. The obtained results prove an important role of oxidative and nitrosative stress in the pathogenesis of EAE, whereas AG and NAC protective effects offer new possibilities for a modified combined approach in MS therapy.
authors: Clinic of Neurology, University Clinical Centre of Nis, Nis, Serbia. srljub@gmail.com
authors: Srdjan
authors: S
authors: Ljubisavljevic
authors: Ivana
authors: I
authors: Stojanovic
authors: Dusica
authors: D
authors: Pavlovic
authors: Dusan
authors: D
authors: Sokolovic
authors: Ivana
authors: I
authors: Stevanovic
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D006146:Guanidines; D009569:Nitric Oxide; D008315:Malondialdehyde; D005620:Freund's Adjuvant; D013482:Superoxide Dismutase; D005978:Glutathione; C004479:pimagedine; D000111:Acetylcysteine