Effect of diphenyl diselenide (DPDS) administered by different via on the development of experimental autoimmune encephalomyelitis (EAE).
EAE is a T cell-mediated inflammatory and demyelinating disease of the central nervous system with clinical and pathological similarities with multiple sclerosis (MS). It can be induced in susceptible animals by a single injection of myelin homogenized in an adequate adjuvant. The oxidative stress is one of the major mediators of demyelination and axonal damage in both, MS and EAE. Therefore, several studies are being performed to assess whether treatment with antioxidants prevents the progression of these diseases. Some organic forms of Se that exhibit glutathione peroxidase-like activity have become good candidates for disease prevention and therapy since they catalytically remove oxidative stressors. Particularly, DPDS exerts antioxidant activity and has neuroprotective effects in several systems. The aim of the present study was to prove the therapeutic activity of DPDS on the development of EAE. DPDS given orally (25 mg/ml in 60% ethanol, 1 ml/kg body weight) produced a significant inhibition of EAE (from 90% to 54% the incidence) without any toxic effect. Intraperitoneally administered DPDS (0.03-7.80 mg/ml in 50% ethanol, 1 ml/kg body weight) reduced also the incidence of the disease but at concentrations higher than 1.5 mg/ml begun to be deleterious for the animals. In addition, there was a higher reactivity of sera from the suppressed animals and diminished DTH and proliferation of mononuclear cells against the encephalitogenic myelin basic protein, indicating a shift from a Th1 to Th2-type milieu. Although more investigation is needed, these results show an effective suppression of the autoimmune response that could be the base for future developments of successful antioxidants therapies in EAE as well as in MS
