Peng Dungeng, Zhang Jinsong, Liu Qingliang, Taylor Ethan Will
School of Chemistry and Materials of Science, University of Science and Technology of China, Hefei 230052, Anhui, PR China.
J Inorg Biochem. 2007 Oct;101(10):1457-63. doi: 10.1016/j.jinorgbio.2007.06.021. Epub 2007 Jun 27.
It has been shown that 36 nm Nano-Se has lower toxicity than selenite or selenomethionine, but these forms of selenium (Se) all possess similar ability to increase selenoenzyme levels. The size of nanoparticles plays an important role in their biological activity: as expected, 5-200 nm Nano-Se can directly scavenge free radicals in vitro in a size-dependent fashion. However, in Se-deficient cells and Se-deficient mice, the size effect of Nano-Se on increasing selenoenzymes and liver Se disappears unexpectedly. We hypothesize that under conditions of Se deficiency, the avidity of Se uptake mechanisms may be increased to maintain the biosynthesis of selenoenzymes, which are fundamental for redox homeostasis. This increased avidity may override the potential advantage of small size Nano-Se seen under Se-replete conditions, thereby eliminating the size effect. Once selenoenzymes have been saturated, Se uptake mechanisms may downregulate; accordingly, the size effect of Nano-Se can then reappear. To test this hypothesis, Se-deficient mice were administered either 36 or 90 nm Nano-Se at supranutritional doses, in both a short-term model and a single-dose model. Under these conditions, Nano-Se showed a size effect on Se accumulation and glutathione S-transferase (GST) activity. A size effect of Nano-Se was found in 15 out of 18 total comparisons between sizes at the same dose and time in the two models. Furthermore, the magnitude of the size effect was more prominent on Se accumulation than on GST activity. GST is strictly regulated by transcriptional and translational mechanisms, so its increase in activity normally does not exceed 3-fold. In contrast, the homeostasis of Se accumulation is not as tightly controlled. In the present experiments, GST activity had reached or was approaching saturation, but liver Se was far below saturation. Therefore, our results strongly suggest that the saturation profile of the tested biomarker has an impact on the size effect of Nano-Se. Since both GST and small molecular weight selenocompounds accumulated in vivo are important intermediates for chemoprevention by Se, our results also suggest that Nano-Se should be most effective as a chemopreventive agent at smaller particle size.
研究表明，36纳米的纳米硒毒性低于亚硒酸盐或硒代蛋氨酸，但这些形式的硒（Se）都具有类似的提高硒酶水平的能力。纳米颗粒的大小在其生物活性中起着重要作用：正如预期的那样，5 - 200纳米的纳米硒能够以大小依赖的方式在体外直接清除自由基。然而，在缺硒细胞和缺硒小鼠中，纳米硒在增加硒酶和肝脏硒含量方面的大小效应意外消失。我们推测，在缺硒条件下，硒摄取机制的亲和力可能会增加，以维持对氧化还原稳态至关重要的硒酶的生物合成。这种增加的亲和力可能会掩盖在富硒条件下看到的小尺寸纳米硒的潜在优势，从而消除大小效应。一旦硒酶饱和，硒摄取机制可能会下调；相应地，纳米硒的大小效应就会再次出现。为了验证这一假设，在短期模型和单剂量模型中，给缺硒小鼠超营养剂量的36纳米或90纳米纳米硒。在这些条件下，纳米硒在硒积累和谷胱甘肽S -转移酶（GST）活性方面表现出大小效应。在两个模型中相同剂量和时间下大小之间的18次总比较中，有15次发现了纳米硒的大小效应。此外，大小效应在硒积累方面比在GST活性方面更为显著。GST受到转录和翻译机制的严格调控，因此其活性增加通常不超过3倍。相比之下，硒积累的稳态控制没有那么严格。在本实验中，GST活性已达到或接近饱和，但肝脏硒含量远低于饱和水平。因此，我们的结果强烈表明，所测试生物标志物的饱和情况对纳米硒的大小效应有影响。由于GST和体内积累的小分子硒化合物都是硒化学预防的重要中间体，我们的结果还表明，纳米硒作为化学预防剂在较小粒径时应该最有效。
