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Hemorrhagic shock/resuscitation involves overwhelming reactive oxygen species (ROS) that cause oxidative stress, inflammation, and subsequent tissue injury. We investigated the effects of the potent antioxidant carboxyfullerene (C 3 ) on acute liver injury during hemorrhage shock/resuscitation. C 3 infusion reduced the alanine aminotransferase (ALT) activity, methemoglobin content, malondialdehyde content, myeloperoxidase activity and expression levels of tumor necrosis factor -α and interleukin-6; it increased superoxide dismutase activity in the liver. The histologic injury score and apoptotic index were also markedly decreased after C 3 treatment compared with the vehicle group. Additionally, C 3 -treated rats showed a significant decrease in nuclear factor-κB DNA binding capacity, which was preceded by reduced phosphorylation of the nuclear factor κB (NF-κB) p65 subunit in the liver. C 3 nanoparticles ameliorate oxidative stress, the inflammatory response, and subsequent acute liver injury after hemorrhagic shock/resuscitation. These protective effects appear to be mediated through the inhibition of the nuclear factor-κB pathway. C 3 treatment may be a promising strategy to improve tissue injury in hemorrhagic shock/resuscitation. [ABSTRACT FROM AUTHOR]