Evaluation of the antioxidant properties of diphenyl diselenide in cultured macrophages and its effects on experimental autoimmune encephalomyelitis

RUPIL LUCIA; CHANADAY NATALI; ROTH GERMAN; DE BEM ANDREZA

Mar del Plata, Buenos Aires

Congreso; LVII Reunión Anual de la Sociedad Argentina de Inmunología; 2009

Sociedad Argentina de Inmunología

A wide range of organoselenium compounds have antioxidant and antiinflammatory activity. Among them, diphenyldiselenide (DPDS) was used to evaluate its antioxidant capacity in vitro, in macrophages (Mf), the cells responsible for the respiratory burst. Peritoneal Mf isolated from Wistar rats and cultured for 48 hs in presence of DPDS showed a decreased viability in a dose-dependent manner, but this effect was absent when the cells were stimulated with bacterial lipopolysaccharides. Besides, we observed a dose-dependent reduction in the levels of nitric oxide produced by normal and stimulated Mf. Furthermore, DPDS showed a tendency to diminish the levels of superoxide anions. Finally, we evaluated the activity of the enzime arginase as a hallmark of antiinflammatory activity, and found that DPDS induced a dose-dependent reduction of this activity. In experimental autoimmune encephalomyelitis, infiltrating Mf and activated microglia are the main cells responsible for the damage of the central nervous system, by the production of cytokines, chemokines and reactive oxygen and nitrogen species. Taking into account the results obtained in vitro, we studied DPDS as a possible preventive treatment for this disease. To accomplish this objective, DPDS was administered orally to Wistar rats previously to the induction of the disease by immunization with an emulsion of bovine myelin and complete Freund`s adjuvant. The analysis of the clinical data obtained, showed a clear supressive effect of the disease, with a diminished incidence from 90% to 54%, without presenting toxic effects. Concomitantly, we observed a decrease in the DTH response, lower proliferation of mononuclear cells to myelin basic protein and a higher reactivity of the sera towards this protein, suggesting a Th2 bias, which leads us to propose DPDS as a possible treatment of autoimmune inflammatory diseases.