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Oxidative Stress

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

¹Department of Physiology, National Taiwan University College of Medicine, Taipei 100; ²Department of Chemistry, National Tsing Hua University, Hsinchu 300; and ³Department of Occupational Safety and Health, College of Health Care and Management, Chung Shan Medical University, Taichung 402, Taiwan

Submitted 4 June 2003 ; accepted in final form 22 December 2003

Fullerene derivatives have often been used as effective scavengers for reactive oxygen species (ROS). This study was designed to test whether polyhydroxylated fullerene derivatives [C₆₀(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 H₂O₂ (400 µM) caused a marked (90%) decrease in cell viability, and this decrease was dose dependently reversed by pretreatment with C₆₀(OH)_7±2 (10–50 µM). The increase in ROS production induced by SNP and H₂O₂ was significantly suppressed by C₆₀(OH)_7±2. Also, the decrease in mitochondrial membrane potential induced by SNP and H₂O₂ was significantly reversed by C₆₀(OH)_7±2. However, high concentration of C₆₀(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 C₆₀(OH)_7±2 (10 mg/kg). These results indicate that polyhydroxylated fullerene derivatives C₆₀(OH)_7±2 at low concentrations protect against oxidative stress in RAW 264.7 cells and IR lungs.

antioxidants; nitric oxide; reactive oxygen species

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