78 results about "Reactive oxygen species generation" patented technology

Methods and compositions useful for neuronal protection in retinal cells in vitro and the protection of mammalian cells from reactive oxygen species in vivo are provided. Ultrafine nano-size cerium oxide particles, less than 10 nanometers in diameter, have been provided to decrease reactive oxygen species (ROS) in retina tissue that generates large amounts of ROS. These reactive oxygen species (ROS) are involved in light-induced retina degeneration and age-related macular degeneration (AMD). Cerium oxide nanoparticles have been used to promote the lifespan of retinal neurons and protect the neurons from apoptosis induced by hydrogen peroxide in vitro and in vivo. The neuronal protection in retinal cells is achieved by decreasing generation of intracellular reactive oxygen species (ROS). Thus, cerium oxide particles are used to promote the longevity of retinal neurons in vitro and mammalian cells in vivo.

The present invention relates to an isoxazole derivative, the compound of formula (I)herein after referred to as GIT27-NO, which is the NO-donating structurally modified form of (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid, herein after referred to as VGX-1027. Treatment of three tumor cell lines, rat astrocytoma C6, mouse fibrosarcoma L929, and mouse melanoma B16 cells with GIT27-NO resulted in a significant reduction of cell respiration and of number of viable cells, while VGX-1027 was completely ineffective. Hemoglobin, which act as NO-scavenger, restored cell viability, thus indicating the NO-mediated tumoricidal effect of compound (I). GIT27-NO triggered apoptotic cell death in L929 cell cultures, while autophagic cell death is mainly responsible for the diminished viability of C6 and B16 cells. Moreover, GIT27-NO induced the production of reactive oxygen species which can be neutralized by antioxidant N-acetyl cysteine (NAC), indicating that reactive oxygen species (ROS) are at least partly involved in the reduction of cell viability. The anti-tumor activity of GIT27-NO is mediated through activation of MAP kinases (ERK1 / 2, p38 and JNK) in cell-specific manner. The role of MAP kinases was further confirmed by specific inhibitors of these molecules, PD98059, SB202190, and SP600125. Finally, in vivo treatment with GIT27-NO significantly reduced tumor growth in syngeneic C57BL / 6 mice implanted with B16 melanoma.