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The polyhydroxylated fullerene derivative C{sub 60}(OH){sub 24} protects mice from ionizing-radiation-induced immune and mitochondrial dysfunction

Journal Article · · Toxicology and Applied Pharmacology
OSTI ID:21344862
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  1. Laboratory of physical Biology, Shanghai Institure of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China)
  2. Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)
  3. Institute of Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University School of Life Science and Technology, Xi'an 710049 (China)
  4. Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington, KY 40536 (United States)

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

OSTI ID:
21344862
Journal Information:
Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 243; ISSN TXAPA9; ISSN 0041-008X
Country of Publication:
United States
Language:
English