Modulation of nitric oxide synthase by arginase and methylated arginines during the acute phase of experimental multiple sclerosis

Abstract

We explore the nitric oxide synthase modulation by methylated arginines, asymmetric (ADMA) and symmetric (SDMA) dimethyl-l-arginine and arginase, in early phase of experimental autoimmune encephalomyelitis (EAE), the most frequently used animal model for studying the multiple sclerosis (MS), during the treatment with selective inducibile nitric oxide synthase inhibitor - aminoguanidine (AG) and oxidative scavenger N-acetyl-l-cysteine (NAC), compared to the clinical signs, continual to our previous research. The given results showed that the arginase activity was significantly increased in EAE rats compared to the healthy and AG treated EAE animals (p<0.05), and it was significantly decreased compared to the NAC treated EAE animals (p<0.05) in examined tissues. The ADMA and SDMA levels were significantly decreased in EAE untreated animals compared to the AG and NAC treated EAE animals (p<0.05). As we have reported in our previous papers, nitric oxide (NO) production, was significantly increased in examined tissues of EAE rats compared to the control group (p<0.05). In AG and NAC treated EAE group NO production was decreased in all tissues compared to untreated EAE animals (p<0.05). Also, the AG and NAC treatment of EAE rats during the development of the disease, significantly decreased the clinical score of EAE treated animals compared to EAE group. Arginase and methylated arginine derivatives, involving also NO, appear to be essential modulators of the inflammatory response in acute phase of MS. The continued research of these findings may provide a new area in the treatment of multiple sclerosis acute phase.