title: The polyhydroxylated fullerene derivative C60(OH)24 protects mice from ionizing-radiation-induced immune and mitochondrial dysfunction.
abstract: Although the protective effect of the polyhydroxylated fullerene derivative C(60)(OH)(n) against ionizing radiation is an area of much interest, the mechanisms relating to how polyhydroxylated fullerene derivatives improve mitochondrial dysfunction remain unknown. In order to find new and effective radioprotective agents, we synthesized a new polyhydroxylated fullerene molecule with 24 hydroxyl groups of known positions on C(60) and studied its protective effects in mice subjected to irradiation. Mice were pretreated with C(60)(OH)(24) for 2 weeks (daily, 40 mg/kg i. p.), then subjected to a lethal dose of whole body gamma-irradiation (from a (60)Co source). Survival was observed for 30 days after irradiation. Immune and mitochondrial dysfunction and oxidative damage were analyzed in mice with the same C(60)(OH)(24) pretreatment and irradiation except that the animals were euthanized at day 5 after the irradiation. It was found that 2-week C(60)(OH)(24) pretreatment effectively reduced whole body irradiation-induced mortality without apparent toxicity. C(60)(OH)(24) pretreatment also showed significant protective effects against ionizing-radiation-induced decreases in immune and mitochondrial function and antioxidant defense in the liver and spleen. These results suggest that the polyhydroxylated fullerene derivative C(60)(OH)(24) protects against ionizing-radiation-induced mortality, possibly by enhancing immune function, decreasing oxidative damage and improving mitochondrial function.
authors.affiliation: Laboratory of physical Biology, Shanghai Institure of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Cai
authors.forename: Jiejie
authors.initials: J
authors.lastname: Hao
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Zhang
authors.forename: Bozhang
authors.initials: B
authors.lastname: Yu
authors.forename: Jinming
authors.initials: J
authors.lastname: Ren
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Qingnuan
authors.initials: Q
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Huang
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D037741:Fullerenes / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008928:Mitochondria / Q000528:radiation effects*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*
chemical_list: D037741:Fullerenes; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species