Iohara Daisuke, Umezaki Yoshitaka, Anraku Makoto, Uekama Kaneto, Hirayama Fumitoshi
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
J Pharm Sci. 2016 Sep;105(9):2959-2965. doi: 10.1016/j.xphs.2016.04.033. Epub 2016 Jun 14.
The objective of this study was to assess the antioxidant ability of C60(OH)10/2-hydroxypropyl-β-cyclodextrin (HP-β-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 C60(OH)10/HP-β-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 C60(OH)10/HP-β-CD nanoparticles was examined on HeLa and HepG2 cells by monitoring the percentage of cell death induced by H2O2. Treatment with C60(OH)10/HP-β-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 C60 (C60(OH)24 and C60(OH)40). The C60(OH)10/HP-β-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 C60(OH)10/HP-β-CD nanoparticles. The results indicate that C60(OH)10/HP-β-CD nanoparticles are a promising antioxidant for use in the treatment of diseases caused by oxidative stresses.
本研究的目的是通过比较C60(OH)10/2-羟丙基-β-环糊精（HP-β-CD）纳米颗粒对活性氮物种的清除能力、在氧化应激条件下的细胞保护作用以及对氧化应激诱导疾病的治疗效果，来评估其抗氧化能力。C60(OH)10/HP-β-CD纳米颗粒对硝酸和过氧亚硝酸根（ONOO(-)）的清除活性高于抗坏血酸、曲洛克斯和依达拉奉等其他抗氧化剂。通过监测H2O2诱导的细胞死亡百分比，研究了C60(OH)10/HP-β-CD纳米颗粒对HeLa和HepG2细胞的细胞保护作用。用C60(OH)10/HP-β-CD纳米颗粒处理可提高细胞活力，这是由于氧化应激受到抑制。此外，与其他多羟基化C60（C60(OH)24和C60(OH)40）相比，这些纳米颗粒具有较高的细胞保护作用。将C60(OH)10/HP-β-CD纳米颗粒静脉注射给对乙酰氨基酚过量诱导肝损伤的小鼠。丙氨酸转氨酶和天冬氨酸转氨酶水平与正常小鼠基本相同，静脉注射C60(OH)10/HP-β-CD纳米颗粒也延长了存活率。结果表明，C60(OH)10/HP-β-CD纳米颗粒是一种有前途的抗氧化剂，可用于治疗由氧化应激引起的疾病。
