ACTA FAC MED NAISS 2014;31(4):233-243

Original article

UDC: 577.175.8:616.8

DOI: 10.2478/afmnai-2014-0029

Benefit Agmatine Effects in Experimental Multiple Sclerosis.

CNS Nitrosative and Oxidative Stress Suppression

Ivana Stojanović¹, Srđan Ljubisavljević^2,3, Ivana Stevanović⁴, Slavica Stojnev⁵, Radmila Pavlović⁶, Dušan Sokolović¹, Aleksandar Petrović⁷, Dušica Pavlović¹, Tatjana Cvetković¹

¹Institute of Biochemistry, University of Niš, Faculty of Medicine, Serbia

²Clinic of Neurology, Clinical Center Niš, Serbia

³Institute of Pathophysiology, University of Niš, Faculty of Medicine, Serbia

⁴Military Medical Academy, Belgrade, Serbia

⁵Institute of Pathology, University of Niš, Faculty of Medicine, Serbia

⁶Department of Pharmacy, University of Niš, Faculty of Medicine, Serbia

⁷Institute of Histology, University of Niš, Faculty of Medicine, Serbia


SUMMARY

The aim of this study was to investigate the exogenous agmatine influence on nitrosative and oxidative stress parameters in acute phase of multiple sclerosis (MS) experimental model, experimental autoimmune encephalomyelitis (EAE). EAE was induced by subcutaneous injection of myelin basic protein (50 µg per animal). Sprague-Dawley rats were divided into five groups: I group - (CG), treated by PBS (i.p.), II group - (EAE), III group - (CFA), treated with Complete Freund’s adjuvant (0.2 ml subcutaneously), IV group - (EAE+AGM), treated by agmatine (75 mg/kg bw i.p.) upon EAE induction and V group - (AGM), received only agmatine in the same dose. The animals were treated every day during experiment – from day 0 to 15, and clinically scored every day. They were sacrificed on day 16 from MBP application. NO2+NO3, S-nitrosothiols (RSNO), malondyaldehide (MDA) and reduced glutathione (GSH) concentrations and superoxide dismutase (SOD) activity were determined in rat whole encephalitic mass (WEM) and cerebellum homogenates. Agmatine exerted strong protective effects on EAE clinical symptoms (p<0.05). In EAE brain homogenates, NO2+NO3, RSNO and MDA concentrations were increased compared to CG values. Agmatine treatment diminished NO2+NO3, RSNO and MDA levels in EAE animals (p<0.05). In EAE rats, GSH level and SOD activity were decreased compared to CG values, but agmatine treatment increased both parameters compared to EAE untreated animals (p<0.05). Immunohistochemical staining supported the clinical and biochemical findings in all groups. The CNS changes in EAE are successfully supressed by agmatine application, which could be the the new aspect of the neuroprotective effects of agmatine.

Key words: EAE, nitric oxide, S-nitrosothiols, malondyledehide, glutathione, superoxide dismutase