Beneficial effect of agmatine in the acute phase of experimental autoimmune encephalomyelitis in iNOS-/- knockout mice

Abstract

The aim of the study was to investigate the hypothesis that agmatine (AGM) provides protection against oxidative stress in experimental autoimmune encephalomyelitis (EAE).Wild-type (WT) and knockout (KO) CBA/H iNOS-/- 3months old (15±5g) mice, were used for EAE induction by myelin basic protein (MBP), dissolved in Complete Freund’s Adjuvant (CFA). The animals were divided into control, EAE, CFA, EAE+AGM and AGM groups. After the development of full clinical remission, animals were decapitated and oxidative stress parameters were determined in whole encephalitic mass (WEM) and cerebellum homogenates.The EAE clinical expression manifested to greater extent in WT than KO mice, was significantly decreased during AGM treatment. We demonstrated significant elevations of superoxide dismutase activity in WT and KO EAE animals, in WEM and cerebellum tissues, which were decreased during AGM treatment in both groups. Superoxide anion content was increased in WEM of both study groups, with a decrease during AGM treatment. The observed changes were more pronounced in WT than in KO animals. Also, the increased expressions of transferrin receptor and glial fibrillary acidic protein observed in WT and KO EAE mice were significantly decreased during AGM treatment.The results suggest potentially beneficial AGM effects in EAE, which might be used for a modified antioxidative approach in MS therapy.