das Neves R Pires, Santos T Margarida, Pereira M de Lourdes, de Jesus J Pedrosa
Department of Biology, University of Aveiro, Portugal.
Hum Exp Toxicol. 2002 Jul;21(7):365-9. doi: 10.1191/0960327102ht243oa.
Chromium toxicity is strongly dependent on its oxidation state. Cr(VI) is carcinogenic and mutagenic, although its in vivo and in vitro toxic effects are related to its intracellular fate. Inside the cells, Cr(VI) is rapidly reduced to stable Cr(III). As Cr(V) and Cr(IV) species have been reported to be formed in the Cr(VI) reduction pathways, Cr(VI)-induced damage is thought, at least in part, to arise from these hypervalent species. The study of Cr(VI) reduction mechanisms and the characterization of the effects of each reactive intermediate constitute important steps towards a better understanding of chromium toxicity. The purpose of this work is to enlarge the scope of Cr(VI)-induced alterations in mouse to other chromium species. Our studies have led to the in situ preparation of a new Cr(V) complex, 1Cr(V)-BT](2-), a stable compound at neutral pH, which mimics Cr(VI) reduction intermediates. The effect of Cr(V) on the histology of mice liver is assessed and compared with similar Cr(VI) assays. Liver toxicity was examined after single administrations of Cr(VI) or Cr(V)-BT to mice. Both compounds produced reversible hepatic damage in a time-dependent manner. However, Cr(V) toxic effects have proved to be more rapid than with Cr(VI), permitting the role of Cr(VI) intermediates formed during intracellular chromium reduction to be highlighted.
铬的毒性很大程度上取决于其氧化态。六价铬具有致癌性和致突变性,尽管其体内和体外毒性作用与其细胞内命运有关。在细胞内,六价铬会迅速还原为稳定的三价铬。由于据报道在六价铬还原途径中会形成五价铬和四价铬物种,所以六价铬诱导的损伤至少部分被认为是由这些高价物种引起的。研究六价铬的还原机制以及表征每种反应中间体的作用是更好地理解铬毒性的重要步骤。这项工作的目的是将小鼠体内六价铬诱导的改变范围扩大到其他铬物种。我们的研究导致原位制备了一种新的五价铬配合物Cr(V)-BT,它在中性pH下是一种稳定的化合物,模拟六价铬还原中间体。评估了五价铬对小鼠肝脏组织学的影响,并与类似的六价铬检测结果进行比较。给小鼠单次施用六价铬或Cr(V)-BT后检查肝脏毒性。两种化合物均以时间依赖性方式产生可逆性肝损伤。然而,已证明五价铬的毒性作用比六价铬更快,这突出了细胞内铬还原过程中形成的六价铬中间体的作用。