Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, Norman Bethune College of Medicine, Jilin University, P. R. China; Department of Pathology, Inner Mongolia Forestry General Hospital, Yakeshi, Inner Mongolia Autonomous Region, P. R. China; Department of Pediatrics, University of Louisville, USA.
Dose Response. 2013;11(1):60-81. doi: 10.2203/dose-response.11-046.Wang. Epub 2011 Dec 2.
Cadmium (Cd) is an important nephrotoxic pollutant. To examine late effects on the kidney of individuals previously exposed to chronic Cd at very low levels, male Wistar rats were given 20 nmol/kg i.p. injections of Cd every other day for 4 weeks. At the 20(th), 28(th), 36(th), 44(th) and 52(nd) week of the study, renal metal accumulation, morphology and function were examined. Immunochemical staining was performed to detect renal 3-nitrotyrosine (3-NT) accumulation, metallothionein (MT) expression, cell proliferation and global DNA methylation. Results showed that renal Cd concentration and MT expression along with 3-NT accumulation were significantly higher in the Cd group than that in the control. Histopathologically renal tubule damage at the early stage and hyperplasia at the late stage were observed in the Cd group. Renal fibrosis in glomeruli was evident in the Cd group, particularly at the late stage of the study. Immunoreactivity of global DNA methylation was markedly diminished in the Cd group at both 20(th) and 52(nd) weeks. These results suggest that previous exposure to chronic Cd at very low level induced persistent damaging effects on the kidney along with increases in cell proliferation and global DNA hypomethylation.
镉（Cd）是一种重要的肾毒性污染物。为了研究以前在极低水平下接触慢性镉的个体对肾脏的晚期影响，雄性 Wistar 大鼠每隔一天接受 20 nmol/kg 的腹腔注射 Cd，共 4 周。在研究的第 20、28、36、44 和 52 周时，检查了肾脏的金属积累、形态和功能。进行免疫化学染色以检测肾脏 3-硝基酪氨酸（3-NT）积累、金属硫蛋白（MT）表达、细胞增殖和整体 DNA 甲基化。结果表明，与对照组相比，Cd 组的肾脏 Cd 浓度和 MT 表达以及 3-NT 积累明显更高。Cd 组在早期观察到肾小管损伤，晚期观察到增生。在 Cd 组中，肾小球的肾纤维化明显，尤其是在研究的后期。在 Cd 组，在第 20 和第 52 周时，整体 DNA 甲基化的免疫反应性明显减弱。这些结果表明，以前在极低水平下接触慢性 Cd 会对肾脏造成持续的损害，同时还会增加细胞增殖和整体 DNA 低甲基化。
