The effects of All-Trans Retinoic Acid on clinical symptoms, nitric oxide levels and total antioxidant capacity of plasma in mouse model of multiple sclerosis

In recent years، increasing evidence suggest that free radicals plays an important role in the pathogenesis of multiple sclerosis and Experimental Autoimmune Encephalomyelitis (EAE)، an animal model of multiple sclerosis. Therefore، All-Trans Retinoic Acid (ATRA) as an antioxidant may be effective in ameliorating disease severity. The present research is an experimental-interventional study. EAE was induced by immunization of female C57BL/6 mice with MOG35-55 peptide and complete Freund''s adjuvant. EAE mice were placed in two therapeutic groups (n=7 per group). Also، 7 mice served as normal (non-EAE) controls. Treatment with ATRA (25mg/Kg-every other day) was initiated in treatment group at day 12 when the treatment group developed a disability score. EAE control received vehicle alone with same schedule. Signs of disease were recorded daily until the day 33 when mice were sacrificed. Then، the levels of nitric oxide in spleen cell culture supernatant and total antioxidant capacity of plasma in mice were evaluated. ATRA significantly alleviated the clinical signs of established EAE. Upon antigen-specific re-stimulation of splenocytes، nitric oxide production was significantly reduced in TRA-treated group and reached in the range of normal mice. In addition، reduction in antioxidant capacity of serum in ATRA-treated EAE mice was prevented. At least part of the beneficial effects of ATRA in the treatment of EAE may be done by suppressing nitric oxide levels and improving antioxidant defense potential.