Heavy metal poisoning: the effects of cadmium on the kidney
Heavy metal poisoning: the effects of cadmium on the kidney
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DOI：
10.1007/s10534-010-9328-y
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发表时间：
2010-10-01
期刊：
影响因子：
3.5
通讯作者：
Unwin, Robert
中科院分区：
文献类型：
--
作者：
Johri, Nikhil;Jacquillet, Gregory;Unwin, Robert
众所周知，重金属镉（Cd）是一种广泛存在的环境污染物，也是一种可能对人类健康产生不利影响的潜在毒素。接触主要通过呼吸道或胃肠道；重要的非工业接触源是香烟烟雾和食物（来自受污染的土壤和水）。肾脏是受慢性镉暴露和毒性影响的主要器官。 Cd 在肾脏中积累，是由于肾近曲小管中受体介导的自由过滤和金属硫蛋白结合的 Cd (Cd-MT) 的内吞作用优先摄取的结果。内化的 Cd-MT 在内体和溶酶体中被降解，将游离 Cd2+ 释放到细胞质中，在细胞质中它可以产生活性氧 (ROS) 并激活细胞死亡途径。慢性镉肾毒性的一个早期且敏感的表现可用于个体和群体筛查，即视黄醇结合蛋白 (RBP) 等低分子量蛋白 (LMWP)（也是近曲小管中受体介导的过程）的重吸收受损。这种所谓的“肾小管蛋白尿”是近端肾小管损伤的良好指标，但通常不能通过常规临床蛋白尿试纸检测来检测。持续大量镉暴露可进展为临床肾范可尼综合征，并最终导致肾衰竭。环境中的镉暴露可能是导致慢性肾脏病发生的一个重要因素，特别是在存在糖尿病或高血压等其他合并症的情况下；因此，镉的来源和环境影响以及限制镉暴露的努力值得更多关注。
The heavy metal cadmium (Cd) is known to be a widespread environmental contaminant and a potential toxin that may adversely affect human health. Exposure is largely via the respiratory or gastrointestinal tracts; important non-industrial sources of exposure are cigarette smoke and food (from contaminated soil and water). The kidney is the main organ affected by chronic Cd exposure and toxicity. Cd accumulates in the kidney as a result of its preferential uptake by receptor-mediated endocytosis of freely filtered and metallothionein bound Cd (Cd-MT) in the renal proximal tubule. Internalised Cd-MT is degraded in endosomes and lysosomes, releasing free Cd2+ into the cytosol, where it can generate reactive oxygen species (ROS) and activate cell death pathways. An early and sensitive manifestation of chronic Cd renal toxicity, which can be useful in individual and population screening, is impaired reabsorption of low molecular weight proteins (LMWP) (also a receptor-mediated process in the proximal tubule) such as retinol binding protein (RBP). This so-called 'tubular proteinuria' is a good index of proximal tubular damage, but it is not usually detected by routine clinical dipstick testing for proteinuria. Continued and heavy Cd exposure can progress to the clinical renal Fanconi syndrome, and ultimately to renal failure. Environmental Cd exposure may be a significant contributory factor to the development of chronic kidney disease, especially in the presence of other co-morbidities such as diabetes or hypertension; therefore, the sources and environmental impact of Cd, and efforts to limit Cd exposure, justify more attention.