In Vitro and In Vivo Evaluation of Hydrophilic C60(OH)10/2-Hydroxypropyl-β-cyclodextrin Nanoparticles as an Antioxidant

In Vitro and In Vivo Evaluation of Hydrophilic C60(OH)10/2-Hydroxypropyl-β-cyclodextrin Nanoparticles as an Antioxidant
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DOI:
10.1016/j.xphs.2016.04.033
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发表时间:
2016-09-01
影响因子:
3.8
通讯作者:
Hirayama, Fumitoshi
Hirayama, Fumitoshi
中科院分区:
医学3区
文献类型:
--
作者:
Iohara, Daisuke;Umezaki, Yoshitaka;Hirayama, Fumitoshi

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本研究的目的是通过比较C-60(OH)(10)/2-羟丙基- β -环糊精(hp - β - cd)纳米颗粒对活性氮的清除能力、氧化应激条件下的细胞保护作用以及对氧化应激诱导的疾病的治疗作用,来评估其抗氧化能力。C-60(OH)(10)/ hp - β - cd纳米颗粒对硝酸和过氧亚硝酸盐(ONOO-)的清除活性高于其他抗氧化剂,如抗坏血酸、trolox和依达拉曲酮。通过监测H2O2诱导HeLa和HepG2细胞死亡的百分比,观察C-60(OH)(10)/ hp - β - cd纳米颗粒对HeLa和HepG2细胞的保护作用。用C-60(OH)(10)/ hp - β - cd纳米颗粒处理后,由于氧化应激的抑制,细胞活力增加。此外,与其他多羟基化的C-60(C-60(OH)(24)和C-60(OH)(40))相比,纳米颗粒具有较高的细胞保护作用。将C-60(OH)(10)/ hp - β - cd纳米颗粒静脉注射给过量对乙酰氨基酚引起的肝损伤小鼠。丙氨酸转氨酶和天冬氨酸转氨酶的水平与正常小鼠基本相同,静脉注射C-60(OH)(10)/ hp - β - cd纳米颗粒也延长了存活率。结果表明,C-60(OH)(10)/ hp - β - cd纳米颗粒是一种很有前途的抗氧化剂,可用于氧化应激引起的疾病的治疗。(C) 2016年由Elsevier Inc.代表美国药剂师协会出版。
The objective of this study was to assess the antioxidant ability of C-60(OH)(10)/2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) nanoparticles, by comparing their scavenging ability for reactive nitrogen species, their cytoprotective effects under conditions of oxidative stress, and their therapeutic effects against diseases that are induced by oxidative stress. The C-60(OH)(10)/HP-beta-CD nanoparticles had a higher scavenging activity against nitric acid and peroxynitrite (ONOO-) than the other antioxidants such as ascorbic acid, trolox, and edaravone. The cytoprotective effect of C-60(OH)(10)/HP-beta-CD nanoparticles was examined on HeLa and HepG2 cells by monitoring the percentage of cell death induced by H2O2. Treatment with C-60(OH)(10)/HP-beta-CD nanoparticles resulted in an increase in cell viability, due to the suppression of the oxidative stress. Furthermore, the nanoparticles had a high cytoprotective effect, compared with other polyhydroxylated C-60 (C-60(OH)(24) and C-60(OH)(40)). The C-60(OH)(10)/HP-beta-CD nanoparticles were intravenously administered to mice with a liver injury induced by an over dose of acetaminophen. Levels of alanine transaminase and aspartate transaminase were essentially the same as those of normal mice and the survival rate was also prolonged by the intravenous administration of the C-60(OH)(10)/HP-beta-CD nanoparticles. The results indicate that C-60(OH)(10)/HP-beta-CD nanoparticles are a promising antioxidant for use in the treatment of diseases caused by oxidative stresses. (C) 2016 Published by Elsevier Inc. on behalf of the American Pharmacists Association.