Fullerene derivatives protect against oxidative stress in RAW 264.7 cells and ischemia-reperfused lungs.

Fullerene derivatives have often been used as effective scavengers for reactive oxygen species (ROS). This study was designed to test whether polyhydroxylated fullerene derivatives [C(60)(OH)(7+/-2)] protect against oxidative stress in cultured RAW 264.7 cells and ischemia-reperfused (IR) lungs. In RAW 264.7 cells, sodium nitroprusside (SNP, 1 mM) and H(2)O(2) (400 microM) caused a marked (90%) decrease in cell viability, and this decrease was dose dependently reversed by pretreatment with C(60)(OH)(7+/-2) (10-50 microM). The increase in ROS production induced by SNP and H(2)O(2) was significantly suppressed by C(60)(OH)(7+/-2). Also, the decrease in mitochondrial membrane potential induced by SNP and H(2)O(2) was significantly reversed by C(60)(OH)(7+/-2). However, high concentration of C(60)(OH)(7+/-2) (1 and 1.5 mM) lead to cell death (apoptosis or necrosis). In the isolated rat lung, the increases in pulmonary artery pressure and capillary filtration pressure induced by SNP during IR were reversed significantly by C(60)(OH)(7+/-2) (10 mg/kg). These results indicate that polyhydroxylated fullerene derivatives C(60)(OH)(7+/-2) at low concentrations protect against oxidative stress in RAW 264.7 cells and IR lungs.