Carboxyfullerene nanoparticles alleviate acute hepatic injury in severe hemorrhagic shock

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-alpha 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-kappa B DNA binding capacity, which was preceded by reduced phosphorylation of the nuclear factor kappa B (NF-kappa B) 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-kappa B pathway. C-3 treatment may be a promising strategy to improve tissue injury in hemorrhagic shock/resuscitation. (C) 2016 Elsevier Ltd. All rights reserved.