Protective effect of reduced glutathione C60 derivative against hydrogen peroxide-induced apoptosis in HEK 293T cells / 华中科技大学学报（医学）（英德文版）

Hydrogen peroxide (H2O2) and free radicals cause oxidative stress, which induces cellular injuries, metabolic dysfunction, and even cell death in various clinical abnormalities. Fullerene (C60) is critical for scavenging oxygen free radicals originated from cell metabolism, and reduced glutathione (GSH) is another important endogenous antioxidant. In this study, a novel water-soluble reduced glutathione fullerene derivative (C60-GSH) was successfully synthesized, and its beneficial roles in protecting against H2O2-induced oxidative stress and apoptosis in cultured HEK 293T cells were investigated. Fourier Transform infrared spectroscopy and (1)H nuclear magnetic resonance were used to confirm the chemical structure of C60-GSH. Our results demonstrated that C60-GSH prevented the reactive oxygen species (ROS)-mediated cell damage. Additionally, C60-GSH pretreatment significantly attenuated H2O2-induced superoxide dismutase (SOD) consumption and malondialdehyde (MDA) elevation. Furthermore, C60-GSH inhibited intracellular calcium mobilization, and subsequent cell apoptosis via bcl-2/bax-caspase-3 signaling pathway induced by H2O2 stimulation in HEK 293T cells. Importantly, these protective effects of C60-GSH were superior to those of GSH. In conclusion, these results suggested that C60-GSH has potential to protect against H2O2-induced cell apoptosis by scavenging free radicals and maintaining intracellular calcium homeostasis without evident toxicity.

Síntesis de fuleeroles a partir de un derivado bromado de c60 / Sythesis of fulllerols from a c60 bromofullerene / Sítese de fúleroois desde um derivado bromado do c60

Se sintetizaron dos Mleroles por hidrólisis básica del compuesto C60Br24 a60°C, con 22 horas de reacción, en presencia de oxígeno atmosférico y utilizando relaciones molares de KOH/C60Br24 de 109 y 184. La geometría inicial no se mantiene al sustituir los átomos de bromo, y los fulleroles obtenidos son de naturaleza aniónica y poseen una estructura compleja que incluye grupos hidroxilo y grupos hemicetal. Se encontró que el tratamiento ácido o el intercambio iónico con resina mixta tipo H+/OH- ocasionan la aparición de grupos carbonilos dentro de su estructura. Los productos se caracterizaron por análisis elemental, espectroscopia infrarroja, UV-Vis, 1H-RMN, MALDI-TOF, TGA y DSC.

Two fullerols were synthesized by means of basic hydrolysis of the compound C60Br24 at 60°C after 22 hours of reaction in presence of atmospheric oxygen, using KOH/ C60Br24 molar ratios of 109 and 184. The initial geometry does not hold upon substitution of Bromine atoms and the obtained fullerols have anionic nature and showed complex structures including hydroxyl groups and hemiketal groups. It was determined that the acid treatment or the ionic exchange with mixed type H+/OH- resin caused the appearance of carbonyl groups in the structure. Products were characterized by elemental analysis, infrared spectroscopy, UV-Vis, MALDI-TOF, 1H-NMR, TGA and DSC.

Sintetizaram-se fulleróis por hidrolise básica do composto C60Br24 a 60°C, com 22 horas de reação, em presença de oxigênio e utilizando relações molares de KOH/ C60Br24 de 109 e 184. A geometria inicial do fullereno bromado não é mantida ao substituir os átomos de bromo. Os fulleróis obtidos são de natureza aniônica e têm uma estrutura complexa que inclui grupos hidroxila e grupos hemicetal. Observou-se que o tratamento ácido ou o intercâmbio iônico com resina tipo H+/OH-, ocasionam a aparição de grupos carbonilas na sua estrutura. Os produtos foram caracterizados por análise elementar, espectroscopia infravermelha, UV-Vis, RMN de 1H, MALDI-TOF, TGA e DSC.