Péterszegi G, Robert A M, Robert L
Laboratoire de Recherche en Ophtalmologie, Faculté de Médecine Broussais-Hôtel Dieu, Université Pierre et Marie Curie (Paris 6), 1, place Parvis Notre Dame, 75181 cedex 4, Paris, France.
Biomed Pharmacother. 2003 May-Jun;57(3-4):130-3. doi: 10.1016/s0753-3322(03)00019-2.
It was shown previously, that millimolar concentrations of ascorbate have cytotoxic and anti-proliferative effects (Eur. J. Clin. Invest. 32 (2002) 372). With increasing concentrations of ascorbate an increasing number of fibroblasts was detached from the culture dish and shown to be lysed by the effect of ascorbate-induced generation of reactive oxygen species (ROS-s). It also could be shown, that this cytotoxic effect is partly due to the dose-dependent inhibition by ascorbate of fibronectin biosynthesis. Superoxide dismutase (SOD) and catalase were shown to salvage cells from ROS-induced cell-death by preventing the inhibition of fibronectin biosynthesis. We used this model system to test the cyto-protective effect of L-fucose and fucose-rich oligo- and polysaccharides (FROP-s). It appeared that relatively low concentrations of L-fucose and FROP-3 (Biomed. Pharmacother. in press) could efficiently protect fibroblasts from the ascorbate-induced cell-death. These novel pharmacological properties of L-fucose and FROP-3 might well be related to their accelerating effect of wound healing.
先前的研究表明,毫摩尔浓度的抗坏血酸具有细胞毒性和抗增殖作用(《欧洲临床研究杂志》32 (2002) 372)。随着抗坏血酸浓度的增加,越来越多的成纤维细胞从培养皿上脱离,并显示因抗坏血酸诱导产生的活性氧(ROS-s)而被裂解。还可以表明,这种细胞毒性作用部分归因于抗坏血酸对纤连蛋白生物合成的剂量依赖性抑制。超氧化物歧化酶(SOD)和过氧化氢酶通过防止纤连蛋白生物合成的抑制作用,使细胞从ROS诱导的细胞死亡中获救。我们使用这个模型系统来测试L-岩藻糖和富含岩藻糖的寡糖及多糖(FROP-s)的细胞保护作用。结果表明,相对低浓度的L-岩藻糖和FROP-3(《生物医学与药物治疗》待发表)能够有效地保护成纤维细胞免受抗坏血酸诱导的细胞死亡。L-岩藻糖和FROP-3的这些新的药理特性很可能与其促进伤口愈合的作用有关。