In dose-response and structure-activity studies, human hepatic HepG2 cells were exposed for 3 days to nano Cu, nano CuO or CuCl₂ (ions) at doses between 0.1 and 30 ug/ml (approximately the no observable adverse effect level to a high degree of cytotoxicity). Various biochemical parameters were then evaluated to study cytotoxicity, cell growth, hepatic function, and oxidative stress. With nano Cu and nano CuO, few indications of cytotoxicity were observed between 0.1 and 3 ug/ml. In respect to dose, lactate dehydrogenase and aspartate transaminase were the most sensitive cytotoxicity parameters. The next most responsive parameters were alanine aminotransferase, glutathione reductase, glucose 6-phosphate dehydrogenase, and protein concentration. The medium responsive parameters were superoxide dismutase, gamma glutamyltranspeptidase, total bilirubin, and microalbumin. The parameters glutathione peroxidase, glutathione reductase, and protein were all altered by nano Cu and nano CuO but not by CuCl₂ exposures. Our chief observations were (1) significant decreases in glucose 6-phosphate dehydrogenase and glutathione reductase was observed at doses below the doses that show high cytotoxicity, (2) even high cytotoxicity did not induce large changes in some study parameters (e.g., alkaline phosphatase, catalase, microalbumin, total bilirubin, thioredoxin reductase, and triglycerides), (3) even though many significant biochemical effects happen only at doses showing varying degrees of cytotoxicity, it was not clear that cytotoxicity alone caused all of the observed significant biochemical effects, and (4) the decreased glucose 6-phosphate dehydrogenase and glutathione reductase support the view that oxidative stress is a main toxicity pathway of CuCl₂ and Cu–containing nanomaterials.

在剂量反应和结构活性研究中，人肝 HepG2 细胞暴露于剂量为0.1 至 30 ug/ml 的纳米 Cu、纳米 CuO 或 CuCl ₂ （离子）中 3 天（大约是未观察到的不良反应水平）高度细胞毒性）。然后评估各种生化参数以研究细胞毒性、细胞生长、肝功能和氧化应激。对于纳米 Cu 和纳米 CuO，在 0.1 至 3 ug/ml 之间几乎没有观察到细胞毒性的迹象。就剂量而言，乳酸脱氢酶和天冬氨酸转氨酶是最敏感的细胞毒性参数。其次最敏感的参数是丙氨酸转氨酶、谷胱甘肽还原酶、葡萄糖 6-磷酸脱氢酶和蛋白质浓度。中等反应参数是超氧化物歧化酶、γ谷氨酰转肽酶、总胆红素和微量白蛋白。谷胱甘肽过氧化物酶、谷胱甘肽还原酶和蛋白质的参数均被纳米Cu和纳米CuO改变，但不被CuCl ₂暴露改变。我们的主要观察结果是（1）在低于显示高细胞毒性的剂量时观察到葡萄糖6-磷酸脱氢酶和谷胱甘肽还原酶显着降低，（2）即使高细胞毒性也不会引起一些研究参数（例如碱性磷酸酶）的大变化、过氧化氢酶、微量白蛋白、总胆红素、硫氧还蛋白还原酶和甘油三酯），（3）尽管许多显着的生化效应仅在显示不同程度细胞毒性的剂量下发生，但尚不清楚细胞毒性是否单独引起了所有观察到的显着生化效应， (4)葡萄糖6-磷酸脱氢酶和谷胱甘肽还原酶的降低支持氧化应激是CuCl ₂和含Cu纳米材料的主要毒性途径的观点。