Metallothionein and antioxidant enzymes in Long-Evans Cinnamon rats treated with zinc
Metallothionein and antioxidant enzymes in Long-Evans Cinnamon rats treated with zinc
复制标题
DOI：
10.1007/s00204-002-0377-z
复制
发表时间：
2002-09-01
影响因子：
6.1
通讯作者：
Irato, P
中科院分区：
文献类型：
--
作者：
Medici, V;Santon, A;Irato, P
Long-Evans Cinnamon (LEC) 大鼠是威尔逊病的突变动物模型。已知这些大鼠的肝脏中铜和铁的异常积累以及血清中铜蓝蛋白和铜的浓度较低。 Cu 的积累可以通过 Cu 转运 P 型 ATP 酶基因的表达缺陷来解释，该基因与威尔逊氏病 (ATP7B) 基因同源。本工作的目的是阐明Zn的作用机制，并在短期治疗实验（1周和2周）中验证Zn对LEC大鼠中Cu、Zn、Fe、金属硫蛋白（MT）、8-羟基-2'-脱氧鸟苷（oh(8)dG）浓度和抗氧化酶活性的作用。众所周知，Zn 可诱导 MT，并具有防止氧化还原活性金属 Cu 和 Fe 与 Zn 金属酶活性位点和蛋白质非特异性结合位点结合并造成氧化损伤的能力。锌的施用通过竞争机制减少铜和铁从粘膜到浆膜肠侧的转运。我们的研究结果表明，醋酸锌治疗会增加组织中 Zn 和 MT 的含量，并降低肝脏和肾脏中 Cu 和 Fe 的浓度，即使肝脏 Zn 和 MT 浓度随着治疗时间的推移而降低。 Zn 诱导 MT 合成有助于减少 Cu 和 Fe 产生的自由基。我们还观察到，肝脏中的超氧化物歧化酶 (SOD) 活性随着治疗时间的延长而降低，与肝脏中铜和铁的减少有关。然而，与未治疗 1 周的大鼠相比，未治疗 2 周的大鼠肾脏中的 SOD 活性有所增加。
The Long-Evans Cinnamon (LEC) rat is a mutant animal model for Wilson's disease. It is known that an abnormal accumulation of Cu and Fe in the liver and low concentrations of both ceruloplasmin and Cu in the serum occur in these rats. The accumulation of Cu is explained by the defective expression of the Cu-transporting P-type ATPase gene, homologous to the gene for Wilson's disease (ATP7B). The aim of this work was to clarify the action mechanism of Zn, and to verify the role that this metal plays in LEC rats in short-term treatment experiments (1 and 2 weeks) on concentrations of Cu, Zn, Fe, metallothionein (MT), 8-hydroxy-2'-deoxyguanosine (oh(8)dG) and on the activity of antioxidant enzymes. It is well known that Zn induces MT and has the ability to prevent redox-active metals, Cu and Fe, binding to and causing oxidative damage at active sites of Zn metalloenzymes and nonspecific binding sites on proteins. Zn administration reduces Cu and Fe transport from mucosal to serosal intestinal sides through competitive mechanisms. Our findings show that treatment with zinc acetate increases tissue Zn and MT contents and decreases Cu and Fe concentrations in the liver and kidneys, even if hepatic Zn and MT concentrations decrease with treatment period. Induction of MT synthesis by Zn contributes to the reduction in free radicals produced by Cu and Fe. We also observed that the superoxide dismutase (SOD)activity in liver decreases with treatment duration in association with the Cu and Fe liver decrease. However, the SOD activity in kidney increases in untreated rats at 2 weeks relative to those untreated for 1 week.