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Antioxidative function and biodistribution of [Gd@C82(OH)22]n nanoparticles in tumor-bearing mice
Authors:Wang Jiangxue  Chen Chunying  Li Bai  Yu Hongwei  Zhao Yuliang  Sun Jin  Li Yufeng  Xing Gengmei  Yuan Hui  Tang Jun  Chen Zhen  Meng Huan  Gao Yuxi  Ye Chang  Chai Zhifang  Zhu Chuanfeng  Ma Baocheng  Fang Xiaohong  Wan Lijun
Affiliation:Lab for Bio-Environmental Health Sciences of Nanoscale Materials and Key Lab of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, P.O. Box 918, Beijing 100049, PR China.
Abstract:Oxidative stress is considered to be one of the important mechanisms involved in carcinogenesis. In our previous study, gadolinium endohedral metallofullerenol ([Gd@C82(OH)22]n nanoparticles) have shown high inhibitory activity on hepatoma cell (H22) growth in mice. To explore the antioxidative functions of nanoparticles, we investigated the biodistribution of [Gd@C82(OH)22]n nanoparticles, the changes of blood coagulation profiles, the metabolism of reactive oxygen species (ROS) in the tumor-bearing mice as well as the possible relationships between nanoparticles treatment and ROS production in this paper. The activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) and catalase (CAT) as well as the levels of reduced glutathione (GSH), protein-bound thiols and malondialdehyde (MDA) were compared between the tumor-bearing mice and normal mice. Transplanted tumors were grown in mice by subcutaneous injection of murine hepatoma cells in the mice. The comparison of the above parameters between nanoparticles and cyclophosphamide (CTX) therapy were also investigated. [Gd@C82(OH)22]n administration can efficiently restore the damaged liver and kidney of the tumor-bearing mice. All the activities of enzymes and other parameters related to oxidative stress were reduced after [Gd@C82(OH)22]n treatment and tended closely to the normal levels. The results suggest that [Gd@C82(OH)22]n nanoparticle treatment could regulate ROS production in vivo.
Keywords:CAT, catalase   CDNB, 1-chlorinechloro-2,4-binitrobenzenedinitrobenzene   CTX, cyclophosphamide   DTNB, 5,5′-dithiobis 2-nitrobenzoic acid   GSH, glutathione   GSH-px, glutathione peroxidase   GST, glutathione S-transferase     0"   alt="  radical dot"   src="  http://cdn.els-cdn.com/sd/entities/rad"   class="  glyphImg"  >OH, hydroxyl radical   H2O2, hydrogen peroxide   ICP-MS, inductively coupled plasma-mass spectrometry   MDA, malondialdehyde   NTP, 2-nitro-5-thiobenzoate anion   1O2, singlet oxygen   O2  0"   alt="  radical dot"   src="  http://cdn.els-cdn.com/sd/entities/rad"   class="  glyphImg"  >, superoxide anions   PBS, phosphate buffer solution   ROS, reactive oxygen species   -SH, protein thiols   SOD, superoxidase dismutase   TBARS, thiobarbituric acid-reactive substance
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