Biological & Medical Research Department, King Faisal Specialist Hospital & Research Centre, PO Box: 3354, Riyadh 11211, Saudi Arabia.
Sci Total Environ. 2012 Aug 1;431:188-96. doi: 10.1016/j.scitotenv.2012.05.036. Epub 2012 Jun 8.
We examined the effect of mercury (Hg) associated with dental amalgam fillings on biomarkers of renal and oxidative stress in children between the ages of 5-15.5 years. Urine samples were analyzed for N-acetyl-β-D-glucosaminidase (NAG), α(1)-microglobulin (α(1)-MG), β(2)-microglobulin (β(2)-MG), retinol binding protein (RBP), albumin (ALB), 8-hydroxy-2-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). The level of urinary Hg (UHg-C) was calculated as μg/g creatinine. Multiple regression analyses revealed that the excretion of urinary NAG was significantly associated with the presence of dental amalgam fillings (β=0.149, P=0.03) and the levels of UHg-C (β=0.531, P=0), with an interaction between the two (P=0). The increase in urinary NAG in relation to UHg-C levels had a dose-effect pattern. The lowest observed effect was seen at UHg-C levels above 1.452 μg/g creatinine, which is lower than previously reported. In contrast, α(1)-MG was negatively associated with the presence of dental amalgam fillings (β=-0.270, P=0), but positively with UHg-C levels (β=0.393, P=0). There were 7 children without, and one child with, dental amalgam fillings with urinary α(1)-MG levels above the reference limit of >7 mg/g creatinine. Even though α(1)-MG seems to be a reliable biomarker for early changes in renal functions, it might exert its effect only at a higher level of exposure. An inverse relationship was also observed between urinary 8-OHdG levels and the presence of dental amalgam fillings. This might suggest that the dental amalgam does not increase DNA damage but reduces the capacity to repair DNA, leading to lower urinary excretion of 8-OHdG. On the other hand, we found that Hg affected the excretion of urinary 8-OHdG in a dose-related pattern that was mostly associated with long-term exposure to low Hg levels. Urinary NAG levels were positively associated with urinary MDA levels (β=0.516, P=0) but not with 8-OHdG (β=0.134, P=0.078) after adjustment for potential confounders. Both UHg-C and the presence of dental amalgam fillings remained predictors of the NAG model. Our data provide evidence that low exposure to Hg from dental amalgam fillings exerts an effect on kidney tubular functions in children. Oxidative stress may have played a role in this mechanism. The results of this study would also suggest that urinary NAG is the most sensitive of all the investigated renal biomarkers. These results should be confirmed with further investigation.
我们研究了汞（Hg）与汞合金填充物对 5-15.5 岁儿童肾脏和氧化应激生物标志物的影响。分析尿液样本中的 N-乙酰-β-D-氨基葡萄糖苷酶（NAG）、α(1)-微球蛋白（α(1)-MG）、β(2)-微球蛋白（β(2)-MG）、视黄醇结合蛋白（RBP）、白蛋白（ALB）、8-羟基-2-脱氧鸟苷（8-OHdG）和丙二醛（MDA）。尿汞（UHg-C）水平以μg/g 肌酐计算。多元回归分析显示，尿 NAG 的排泄与存在汞合金填充物（β=0.149，P=0.03）和 UHg-C 水平（β=0.531，P=0）显著相关，两者之间存在相互作用（P=0）。与 UHg-C 水平相关的尿 NAG 增加呈剂量效应模式。在 UHg-C 水平高于 1.452μg/g 肌酐时，观察到的最低效应，这低于先前的报告。相比之下，α(1)-MG 与汞合金填充物的存在呈负相关（β=-0.270，P=0），但与 UHg-C 水平呈正相关（β=0.393，P=0）。有 7 名儿童没有、1 名儿童有汞合金填充物，其尿 α(1)-MG 水平高于>7mg/g 肌酐的参考限值。尽管 α(1)-MG 似乎是肾功能早期变化的可靠生物标志物，但它可能仅在更高的暴露水平下发挥作用。尿液 8-OHdG 水平与汞合金填充物的存在之间也存在反比关系。这可能表明，汞合金不会增加 DNA 损伤，而是降低修复 DNA 的能力，导致尿液中 8-OHdG 的排泄减少。另一方面，我们发现 Hg 以剂量相关的模式影响尿 8-OHdG 的排泄，这主要与长期接触低水平 Hg 有关。调整潜在混杂因素后，尿 NAG 水平与尿 MDA 水平呈正相关（β=0.516，P=0），但与 8-OHdG 水平无相关性（β=0.134，P=0.078）。UHg-C 和汞合金填充物的存在仍然是 NAG 模型的预测因子。我们的数据提供了证据，表明来自汞合金填充物的低水平 Hg 暴露会对儿童的肾小管功能产生影响。氧化应激可能在这一机制中发挥了作用。本研究的结果还表明，尿 NAG 是所有研究的肾生物标志物中最敏感的。这些结果需要进一步研究加以证实。
