Irato Paola, Albergoni Vincenzo
Department of Biology, Via U. Bassi 58/B, University of Padua, 35121 Padua, Italy.
Chem Biol Interact. 2005 Aug 15;155(3):155-64. doi: 10.1016/j.cbi.2005.06.005.
The effectiveness of Zn at moderating the pro-oxidant effects of Cu was evaluated in two rat models that differed in the route and mode of administration. The endpoints investigated included measurement of the concentrations of Cu, Zn, metallothionein and glutathione concentrations, as well as SOD and catalase activity, in liver, kidneys and intestine. In a sub-chronic animal model, the hepatic accumulation of Cu was achieved by administration of dietary Cu (1.8 g/kg solid diet) for 30 days after which oral Zn (6g/kg solid diet) was given. Cu treatment induced an increase in the hepatic and intestinal concentration of Cu of 66 and 455%, respectively, that was not associated with synthesis of metallothionein synthesis, but rather appeared to be related to the higher activity of SOD. Subsequent administration with Zn after dietary Cu induced an increase in the hepatic and intestinal metallothionein content of more twice and reduced the Cu content to control values. Thus, Zn could act as both a competitor for absorption on the luminal side of the intestinal epithelium inducing the synthesis of metallothionein. In the second animal model, we studied the effects of interaction between Cu and Zn administered by i.p. injection at the dose of 3 and 10mg/kg, respectively; Zn was administered subsequent to Cu overload. In this case, when Zn was administered, Cu was already deposited in tissues and thus there is no competition between two metals at the level of membrane transport. In this experimental model treatment with Cu alone induced liver metallothionein synthesis, and the subsequent treatment with Zn did not decrease the hepatic content of Cu. One explanation for these observations is that Zn induces the synthesis of metallothionein, which binds Cu for which it has a higher affinity. Moreover, after treatment with Zn, SOD activity in the liver decreases of almost 30% with respect to treatment with alone Cu, suggesting that Zn has a protective effect.
在两种给药途径和方式不同的大鼠模型中，评估了锌对铜促氧化作用的调节效果。研究的终点指标包括测量肝脏、肾脏和肠道中铜、锌、金属硫蛋白和谷胱甘肽的浓度，以及超氧化物歧化酶（SOD）和过氧化氢酶的活性。在一个亚慢性动物模型中，通过给予含铜饮食（1.8 g/kg固体饮食）30天来实现肝脏中铜的蓄积，之后口服锌（6 g/kg固体饮食）。铜处理导致肝脏和肠道中铜的浓度分别增加了66%和455%，这与金属硫蛋白的合成无关，而似乎与SOD的较高活性有关。在给予含铜饮食后随后给予锌，导致肝脏和肠道中金属硫蛋白含量增加了两倍多，并将铜含量降低至对照值。因此，锌可以作为肠道上皮腔侧吸收的竞争者，诱导金属硫蛋白的合成。在第二个动物模型中，我们研究了分别以3和1０mg/kg剂量腹腔注射铜和锌之间相互作用的影响；在铜过载后给予锌。在这种情况下，当给予锌时，铜已经沉积在组织中，因此在膜转运水平上两种金属之间没有竞争。在这个实验模型中，单独用铜处理诱导肝脏金属硫蛋白合成，随后用锌处理并没有降低肝脏中的铜含量。对这些观察结果的一种解释是，锌诱导金属硫蛋白的合成，金属硫蛋白结合与其具有更高亲和力的铜。此外，与单独用铜处理相比，用锌处理后肝脏中的SOD活性降低了近30%，这表明锌具有保护作用。
