Kachesova P S, Goroshinskaja I A, Borodulin V B, Shalashnaja E V, Chudilova A V, Nemashkalova L A
Rostov Research Institute of Oncology, Rostov-on-Don, Russia.
Biomed Khim. 2016 Jul;62(5):555-560. doi: 10.18097/PBMC20166205555.
The use of metal nanoparticles (NPs) for cancer treatment requires careful examination of their biological effects. The aim of this study was to determine parameters of oxidative processes in the blood of tumor-bearing animals treated with metallic iron NPs only. The markers of antioxidant status and accumulation of lipid peroxidation products were measured in erythrocytes and blood plasma of rats with Pliss lymphosarcoma (PLS) and intact rats. PLS animals were treated eight times with iron NPs (at a dose of 1.25 mg/kg bw (main group), rats of the control group received saline (0.3 ml). In control animals, an increase in malondialdehyde (MDA) was observed in red blood cells (RBC) by 45%; this was accompanied by compensatory increase in reduced glutathione (GSH) and catalase by 24% and 14.3%, respectively (p<0.05). In plasma an increase in MDA by 167.4% (p<0.01) and a decrease in oxidase activity of ceruloplasmin (CP) by 36.8% (p<0.001) were found. In the main group there was a decrease of accumulation of lipid peroxidation products in the blood. Intensity of detected changes depended on the antitumor effect: rats with growing LSP showed a tendency to the decrease in the RBC MDA level and normalization of plasma MDA; in animals with LSP regression this marker did not differ from normal values. In all animals of the main group the CP content was basically the same as in intact rats while GSH increased in the group without therapeutic effect (by 218.6%) and in the group with the effect by 69% (versus normal values; p<0.01). SOD activity in the rats with LSP growth significantly increased (by 42%), in the rats with regression decreased (by 30%) with subsequent normalization. Thus, administration of iron NPs caused activation of the antioxidant system in blood and a significant decrease in the manifestations of oxidative stress associated with tumor growth.
使用金属纳米颗粒(NPs)进行癌症治疗需要仔细研究其生物学效应。本研究的目的是确定仅用金属铁纳米颗粒治疗的荷瘤动物血液中氧化过程的参数。在患有普利斯淋巴肉瘤(PLS)的大鼠和正常大鼠的红细胞和血浆中测量抗氧化状态标志物和脂质过氧化产物的积累。PLS动物用铁纳米颗粒治疗八次(剂量为1.25mg/kg体重,主要组),对照组大鼠接受生理盐水(0.3ml)。在对照动物中,红细胞(RBC)中丙二醛(MDA)增加45%;同时,还原型谷胱甘肽(GSH)和过氧化氢酶分别代偿性增加24%和14.3%(p<0.05)。在血浆中,发现MDA增加167.4%(p<0.01),铜蓝蛋白(CP)氧化酶活性降低36.8%(p<0.001)。在主要组中,血液中脂质过氧化产物的积累减少。检测到的变化强度取决于抗肿瘤作用:LSP生长的大鼠红细胞MDA水平有下降趋势,血浆MDA正常化;在LSP消退的动物中,该标志物与正常值无差异。主要组所有动物的CP含量与正常大鼠基本相同,而在无治疗效果的组中GSH增加(218.6%),在有治疗效果的组中增加69%(与正常值相比;p<0.01)。LSP生长的大鼠中超氧化物歧化酶(SOD)活性显著增加(42%),消退的大鼠中SOD活性降低(30%),随后恢复正常。因此,给予铁纳米颗粒可激活血液中的抗氧化系统,并显著降低与肿瘤生长相关的氧化应激表现。