The natural organosulfur compound dipropyltetrasulfide prevents HOCL-induced systemic sclerosis in the mouse

Abstract

Introduction: The aim of this study was to test the naturally occurring organosulfur compound dipropyltetrasulfide (DPTTS) found in plants, which has antibiotic and anti-cancer properties, as a treatment of HOCl-induced systemic sclerosis in the mouse. Methods: The pro-oxidative, anti-proliferative and cytotoxic effects of DPTTS were evaluated ex vivo on fibroblasts from normal and HOCl-mice. In vivo, the anti-fibrotic and immunomodulating properties of DPTTS were evaluated in the skin and lungs of HOCl-mice. Results: H2O2 production was higher in fibroblasts derived from HOCl-mice than in normal fibroblasts (P<0.05). DPTTS did not increase H2O2 production in normal fibroblasts, but DPTTS dose-dependently increased H2O2 production in HOCl-fibroblasts (P<0.001 with 40μM DPTTS). Because H2O2 reached a lethal threshold in cells from HOCl-mice, the anti-proliferative, cytotoxic and pro-apoptotic effects of DPTTS were significantly higher in HOCl-fibroblasts than for normal fibroblasts. In vivo, DPTTS decreased dermal thickness (P<0.001), collagen content in skin (P<0.01) and lungs (P<0.05), SMA (P<0.01) and pSMAD2/3 (P<0.01) expression in skin, formation of advanced oxidation protein products and anti-DNA topoisomerase-1 antibodies in serum (P<0.05) versus untreated HOCl- mice. Moreover, in HOCl-mice, DPTTS reduced splenic B cell counts (P<0.01), the proliferative rates of B-splenocytes stimulated by lipopolysaccharide (P<0.05) and T-splenocytes stimulated by anti-CD3/CD28 mAb (P<0.001). Ex vivo, it also reduced the production of IL-4 and IL-13 by activated T cells (P<0.05 in both cases). Conclusions: The natural organosulfur compound DPTTS prevents skin and lung fibrosis in the mouse through the selective killing of diseased fibroblasts and its immunomodulating properties. DPTTS may be a potential treatment of Systemic sclerosis.