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

doi:10.1016/j.taap.2009.11.009

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

Toxicology and Cancer Biology

Research output: Contribution to journal › Article › peer-review

79 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 language	English
Pages (from-to)	27-34
Number of pages	8
Journal	Toxicology and Applied Pharmacology
Volume	243
Issue number	1
DOIs	https://doi.org/10.1016/j.taap.2009.11.009
State	Published - 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

Access to Document

10.1016/j.taap.2009.11.009

Cite this

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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 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.",

keywords = "Antioxidant, Apoptosis, Mortality, Oxidative damage, Radioprotection, Reactive oxygen species",

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

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.",

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T1 - The polyhydroxylated fullerene derivative C60(OH)24 protects mice from ionizing-radiation-induced immune and mitochondrial dysfunction

AU - Cai, Xiaoqing

AU - Hao, Jiejie

AU - Zhang, Xiaoyong

AU - Yu, Bozhang

AU - Ren, Jinming

AU - Luo, Cheng

AU - Li, Qingnuan

AU - Huang, Qing

AU - Shi, Xianglin

AU - Li, Wenxin

AU - Liu, Jiankang

N1 - 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.

PY - 2010/2/15

Y1 - 2010/2/15

N2 - 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.

AB - 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.

KW - Antioxidant

KW - Apoptosis

KW - Mortality

KW - Oxidative damage

KW - Radioprotection

KW - Reactive oxygen species

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