Transport of cadmium and manganese in mammals

采用离体和体内两种方法研究了锰转运系统在镉积累和毒性中的作用。同时添加Mn或Zn可抑制MT缺失细胞中Cd的积累，并呈剂量依赖性。与此同时，镉的细胞毒性被抑制锰和锌剂量依赖性，这表明具有高亲和力的镉，锰和锌的运输系统中起着重要的作用，镉掺入细胞。在小鼠中，锰或钴与镉同时给药显示镉引起的肝毒性和睾丸出血显着减少。金属硫蛋白基因敲除小鼠也观察到这些影响，这表明金属硫蛋白不参与锰和钴的保护。然而，组织镉浓度没有改变，通过共同管理的锰或钴与镉。虽然Mn和Co对Cd毒性的保护作用不能通过Cd在组织中积累的变化来解释，但IL-6在保护Cd毒性中的新作用有牵连。这些数据表明，锰是参与镉在特定的细胞系，但不是所有的哺乳动物细胞的沉积和毒性。细胞因子，特别是IL-6的参与，在体内锰和钴对镉毒性的影响，应在未来的研究中澄清。

The roles of Mn transport system on the accumulation and toxicity of Cd were studied using both in vitro and in vivo systems. Cellular accumulation of Cd in MT null cells was inhibited by simultaneous addition of Mn or Zn in the medium dose-dependently. In parallel, cytotoxicity of Cd was inhibited by Mn and Zn dose-dependently, suggesting that the transport system having high affinity for Cd, Mn and Zn plays an important role in Cd incorporation into cells. In mice, simultaneous administration of Mn or Co with Cd showed marked decreases in hepatotoxicity and testicular hemorrhage caused by Cd. These effects were also observed in metallothionein knockout mice, suggesting that metallothionein is not involved in the protection by Mn and Co. However, tissue Cd concentrations were not altered, by co-administration of Mn or Co with Cd. Although protective effects of Mn and Co on Cd toxicity were not explained by the change in tissue accumulation of Cd, a novel role of IL-6 in the protection against Cd toxicity was implicated. These data suggest that Mn is involved in the deposition and toxicity of Cd in specific cell lines but not all cells of mammals. Involvement of cytokine, especially IL-6, in in vivo effects of Mn and Co on Cd toxicity should be clarified in future studies.