Pu Xinzhu, Wang Zemin, Zhou Shaoyu, Klaunig James E
Biomolecular Research Center, Boise State University, Idaho, USA, 47408.
Department of Environmental Health, Indiana University School of Public Health, Bloomington, Indiana, 47408.
Environ Toxicol. 2016 Dec;31(12):1808-1818. doi: 10.1002/tox.22182. Epub 2015 Sep 2.
The induction of oxidative stress and damage appears to be involved in acrylonitrile induction of brain astrocytomas in rat. The present study examined the effects of dietary antioxidant supplementation on acrylonitrile-induced oxidative stress and oxidative damage in rats in vivo. To assess the effects of antioxidants on biomarkers of acrylonitrile-induced oxidative stress, female F344 rats were provided with diets containing vitamin E (0.05%), green tea polyphenols (GTP, 0.4%), N-acetyl cysteine (NAC, 0.3%), sodium selenite (0.1mg/kg), and taurine (10g/kg) for 7 days, and then co-administered with 0 and 100 ppm acrylonitrile in drinking water for 28 days. Significant increase in oxidative DNA damage in brain, evidenced by elevated 8OHdG levels, was seen in acrylonitrile-exposed rats. Supplementation with vitamin E, GTP, and NAC reduced acrylonitrile-induced oxidative DNA damage in brain while no protective effects were seen with the selenium or taurine supplementation. Acrylonitrile increased oxidative DNA damage, measured by the fpg-modified alkaline Comet assay in rat WBCs, which was reduced by supplementation of Vitamin E, GTP, NAC, selenium, and taurine. In addition to stimulation of oxidative DNA damage, acrylonitrile triggered induction of pro-inflammatory cytokines Tnfα, Il-1β, and Ccl2, and the growth stimulatory cyclin D1 and cyclin D2 genes, which were effectively down-regulated with antioxidant treatment. Antioxidant treatment also was able to stimulate the pro-apoptotic genes Bad, Bax, and FasL and DNA repair genes Xrcc6 and Gadd45α. The results of this study support the involvement of oxidative stress in the development of acrylonitrile-induced astrocytomas and suggest that antioxidants block acrylonitrile-mediated damage through mechanisms that may involve in the suppression of inflammatory responses, inhibition of cell proliferation and stimulation of apoptosis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1808-1818, 2016.
氧化应激和损伤的诱导似乎与大鼠脑中丙烯腈诱导的星形细胞瘤有关。本研究检测了膳食补充抗氧化剂对体内丙烯腈诱导的大鼠氧化应激和氧化损伤的影响。为评估抗氧化剂对丙烯腈诱导的氧化应激生物标志物的影响，给雌性F344大鼠提供含维生素E（0.05%）、绿茶多酚（GTP，0.4%）、N-乙酰半胱氨酸（NAC，0.3%）、亚硒酸钠（0.1mg/kg）和牛磺酸（10g/kg）的饮食7天，然后在饮用水中同时给予0和100ppm的丙烯腈，持续28天。在接触丙烯腈的大鼠中，脑内氧化DNA损伤显著增加，表现为8OHdG水平升高。补充维生素E、GTP和NAC可降低丙烯腈诱导的脑内氧化DNA损伤，而补充硒或牛磺酸则未见保护作用。通过fpg修饰的碱性彗星试验检测，丙烯腈增加了大鼠白细胞中的氧化DNA损伤，补充维生素E、GTP、NAC、硒和牛磺酸可降低该损伤。除了刺激氧化DNA损伤外，丙烯腈还引发了促炎细胞因子Tnfα、Il-1β和Ccl2以及生长刺激细胞周期蛋白D1和细胞周期蛋白D2基因的诱导，而抗氧化剂处理可有效下调这些基因。抗氧化剂处理还能够刺激促凋亡基因Bad、Bax和FasL以及DNA修复基因Xrcc6和Gadd45α。本研究结果支持氧化应激参与丙烯腈诱导的星形细胞瘤的发生发展，并表明抗氧化剂通过可能涉及抑制炎症反应、抑制细胞增殖和刺激凋亡的机制来阻断丙烯腈介导的损伤。©2015威利期刊公司。《环境毒理学》31:1808 - 1818，2016。
