Zhou D, Chen Z J, Hu G P, Yan T L, Long C M, Feng H M, Jia G
Beijing Da Xue Xue Bao Yi Xue Ban. 2020 Oct 18;52(5):821-827. doi: 10.19723/j.issn.1671-167X.2020.05.005.
To evaluate the sub-acute oral effect of titanium dioxide (TiO) nanoparticles on the oxidation/antioxidation biomarkers and inflammatory cytokines in blood, liver, intestine, and colon in rats.
Twenty four 4-week-old clean-grade Sprague Dawley (SD) rats were randomly devided into 4 groups by body weight (=6, control, low, middle, and high), in which the rats were orally exposed to TiO nanoparticles at doses of 0, 2, 10 and 50 mg/kg body weight/day for 28 consecutive days separately. Food intake, body weight and abnormal behaviors during the experiment were recorded. The rats were euthanized on the 29th day. The blood was collected abdominal aortic method and centrifuged to collect the serum. Tissues from liver, intestine and colon were collected and homogenated. Then enzyme-linked immunosorbent assay (ELISA) and microwell plate methods were used to detect oxidation/antioxidation biomarkers including superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), total mercapto (T-SH), glutathione disulfide (GSSG), malomdialdehvde (MDA) and inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the serum, liver, intestine and colon in the rats.
Compared with the control group, no significant differences in body weight, food intake and organ coefficients were observed in all the three groups after TiO gavage. No significant changes in GSH, GSH-Px, T-SH, and IL-6 were observed. Compared with the control group, significant increase of SOD activity in serum in high dose group, signi-ficant increase of GSSG concentration in intestine in middle and high dose group and significant increase of MDA concentration in liver in low and high dose group were observed. Compared with the control group, a significant increase of TNF-α in liver in middle and high dose group was observed.
TiO nanoparticle can increase antioxidant enzymes activities in blood, increase oxidative biomarkers in liver and intestine, increase inflammatory cytokines in liver in rats after a 28-day sub-acute orally administration. Among blood, liver, intestine, and colon, liver is most sensitive to the toxicity induced by TiO nanoparticles, followed by intestine, blood, and colon in sequence.
评估二氧化钛(TiO)纳米颗粒对大鼠血液、肝脏、肠道和结肠中氧化/抗氧化生物标志物及炎性细胞因子的亚急性口服效应。
将24只4周龄清洁级Sprague Dawley(SD)大鼠按体重随机分为4组(每组6只,分别为对照组、低剂量组、中剂量组和高剂量组),大鼠分别按0、2、10和50 mg/kg体重/天的剂量连续28天经口暴露于TiO纳米颗粒。记录实验期间的食物摄入量、体重和异常行为。在第29天对大鼠实施安乐死。采用腹主动脉采血法采集血液并离心收集血清。收集肝脏、肠道和结肠组织并匀浆。然后采用酶联免疫吸附测定(ELISA)和微孔板法检测大鼠血清、肝脏、肠道和结肠中氧化/抗氧化生物标志物,包括超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)、总巯基(T-SH)、谷胱甘肽二硫化物(GSSG)、丙二醛(MDA)以及炎性细胞因子,包括白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)。
与对照组相比,TiO灌胃后所有三组大鼠的体重、食物摄入量和器官系数均无显著差异。GSH、GSH-Px、T-SH和IL-6未观察到显著变化。与对照组相比,高剂量组血清中SOD活性显著升高,中剂量组和高剂量组肠道中GSSG浓度显著升高,低剂量组和高剂量组肝脏中MDA浓度显著升高。与对照组相比,中剂量组和高剂量组肝脏中TNF-α显著升高。
经28天亚急性口服给药后,TiO纳米颗粒可增加大鼠血液中的抗氧化酶活性,增加肝脏和肠道中的氧化生物标志物,增加肝脏中的炎性细胞因子。在血液、肝脏、肠道和结肠中,肝脏对TiO纳米颗粒诱导的毒性最敏感,其次依次为肠道、血液和结肠。