Abstract
Ischemia/reperfusion injury (IRI), resulting from hypoxic damage within a graft, is the leading cause of cell death and graft rejection. In this study, we investigated whether a HIF-1α inhibitor or various antioxidants were able to prevent ischemic injury in a cellular model in which experimental hypoxia was induced using CoCl2. The ischemic injury induced in HK-2 cells by CoCl2 was validated by increased reactive oxygen species (ROS) production, reduced cell viability, and increased apoptosis at different times and doses. The preventative effects of various anti-oxidants on ischemic injury were evaluated using ROS levels, cell viability, and apoptosis. The MAPK phosphorylation status and Bcl2/Bax expression levels were evaluated after treatment with various antioxidants. The increase in ROS induced by hypoxia was significantly inhibited by NAC and CAPE, but not by any other treatment. The reduction in cell viability induced by CoCl2 was significantly inhibited by NAC and DPI, but not by any other treatment. The apoptosis induced by CoCl2 was also significantly inhibited by NAC and DPI, but not by any other treatment. Moreover, NAC and DPI prevented CoCl2-induced apoptosis in HK-2 cells in a dose- and time-dependent manner. Treatment of CoCl2 and HK-2 cells treated with DPI, but not NAC, significantly induced ERK activation and Bcl2 expression. NAC and DPI treatment prevented the apoptosis of cells cultured under hypoxic conditions. Our results suggest that DPI should be investigated further as a novel protective agent that prevents kidney ischemia.
Published Version
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