Anti-apoptosis effect of amino acid modified gadofullerene via mitochondria mediated pathway

The metallofullerene Gd@C82 derivatives have been found to exhibit excellent performance in chronic diseases treatment and tumor therapy by their excellent anti-oxidation capability. Thus, there is great need to clarify the specific protection mechanism of Gd@C82 derivatives against oxidative stress in cellular and molecular level. Herein, we optimized the preparation of amino acid derivatives of Gd@C82 (GF-Ala) and investigated the potential mechanism of anti-oxidative stress induced by H2O2 in L02 human hepatic cells. GF-Ala of excellent biocompatibility and high production yield was obtained by adjusting the size of solid Gd@C82 as starting material. Pretreatment with GF-Ala significantly improved cell viability of oxidative damaged cells. Furthermore, we found that GF-Ala prominently reduced intracellular reactive oxygen species (ROS) production, stabilized mitochondria membrane potential (MMP) and inhibited cell apoptosis. Moreover, GF-Ala up-regulated the expression of Bcl-2 and down-regulated the expression of Bax, which further prevented the activation of pro-caspase 3 and PARP. Therefore, we revealed that GF-Ala protected cells from oxidative stress by blocking the mitochondria-mediated apoptosis pathway.