The polyhydroxylated fullerene derivative C60(OH)24 protects mice from ionizing-radiation-induced immune and mitochondrial dysfunction

Xiaoqing Cai, Jiejie Hao, Xiaoyong Zhang, Bozhang Yu, Jinming Ren, Cheng Luo, Qingnuan Li, Qing Huang, Xianglin Shi, Wenxin Li, Jiankang Liu

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Although the protective effect of the polyhydroxylated fullerene derivative C60(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 C60 and studied its protective effects in mice subjected to irradiation. Mice were pretreated with C60(OH)24 for 2 weeks (daily, 40 mg/kg i. p.), then subjected to a lethal dose of whole body γ-irradiation (from a 60Co source). Survival was observed for 30 days after irradiation. Immune and mitochondrial dysfunction and oxidative damage were analyzed in mice with the same C60(OH)24 pretreatment and irradiation except that the animals were euthanized at day 5 after the irradiation. It was found that 2-week C60(OH)24 pretreatment effectively reduced whole body irradiation-induced mortality without apparent toxicity. C60(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 C60(OH)24 protects against ionizing-radiation-induced mortality, possibly by enhancing immune function, decreasing oxidative damage and improving mitochondrial function.

Original languageEnglish
Pages (from-to)27-34
Number of pages8
JournalToxicology and Applied Pharmacology
Volume243
Issue number1
DOIs
StatePublished - Feb 15 2010

Bibliographical note

Funding Information:
This study was supported by grants from the special project of Shanghai Nano-technology 0552nm033 , 0652nm016 and 0752nm021 (W. L.). MOST973 program No. 2006CB705605 (W.L.), the Ministry of Health ( 2009ZX10004-301 ), the Shanghai Municipal Natural Science Foundation ( 08ZR1422700 , 08JC1422600 ) and the Shanghai Science and Technical Committee (J.L.), the Chinese Academy of Sciences (J.L.), National Natural Science Foundation of China Key Program No. 30930105 and Xi'an Jiaotong University (J.L.). This study was partially supported by NIH grants, 5R01 CA119028-05, R01 CA116697, R01 ES015518, and R01 ES015375.

Keywords

  • Antioxidant
  • Apoptosis
  • Mortality
  • Oxidative damage
  • Radioprotection
  • Reactive oxygen species

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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