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[铅暴露生化标志物综述,特别关注血红素和核苷酸代谢]

[Reviews on biochemical markers of lead exposure with special emphasis on heme and nucleotide metabolisms].

作者信息

Sakai T

机构信息

Center of Occupational Medicine, Tokyo Labor Accident Hospital, Japan.

出版信息

Sangyo Eiseigaku Zasshi. 1995 Mar;37(2):99-112. doi: 10.1539/sangyoeisei.37.2_99.

Abstract

Biochemical marker in heme and nucleotide metabolisms were reviewed and evaluated in terms of biological monitoring of lead exposure. Analytical methods, reference values, threshold values, dose-effect relationships, validity, applicable range of Pb-B levels, and confounding factors were studied for the biochemical parameters: delta-aminolevulinic acid dehydratase activity (ALA-D), delta-aminolevulinic acid in plasma (ALA-P), delta-aminolevulinic acid in urine (ALA-U), coproporphyrin in urine (CP-U), erythrocyte protoporphyrin (EP) or zinc protoporphyrin (ZP), pyrimidine 5'-nucleotidase (P5N), and pyrimidine nucleotides in blood (PN). The threshold value of Pb-B for ALA-D by CEC method or restoration method was 5 micrograms/dl. The high validity (> 1.8) was found at a wide range of Pb-B levels between 5 and 50 micrograms/dl, while that of ALA-D activity by CEC method was between 20 and 50 micrograms/dl. The threshold value of Pb-B for ALA-P was also as low as 5 micrograms/dl, and that for ALA-U (corrected for creatinine) was between 15 and 30 micrograms/dl or 20 and 40 micrograms/dl in HPLC or colormetric method, respectively. ALA-P showed a high validity (> 1.8) at Pb-B levels of 30 and 60 micrograms/dl, whereas ALA-U did at Pb-B of 60 micrograms/dl alone. EP (ZP) and CP-U were significantly increased in the Pb-B levels higher than 20 to 30 micrograms/dl and 40 micrograms/dl, respectively. The threshold level of Pb-B for P5N activity was less than 10 micrograms/dl, and showed a linear reduction in activity with a rise in Pb-B values between 10 and 60 micrograms/dl. The validity of P5N (1.86 at a cut off of < 10 mumol/h/g Hb) was the highest among biochemical parameters examined at Pb-B values over 40 micrograms/dl. PN was increased in the Pb-B levels higher than 60 micrograms/dl. Individual variation of ALA-U, CP-U, and ZP were relatively larger than those of PN. ALA-P seemed to be one of the most desirable biomarkers for lead exposure, because of simplicity, sensitivity and specificity of analytical method, and of wide range of applicable Pb-B, from normal to intoxication levels. PN might be of diagnostic value for lead intoxication. Lead effect or intoxication could be assessed more exactly by the combination of some specific biomarkers mentioned above.

摘要

从铅暴露的生物监测角度,对血红素和核苷酸代谢中的生化标志物进行了综述和评估。研究了以下生化参数的分析方法、参考值、阈值、剂量-效应关系、有效性、血铅水平的适用范围以及混杂因素:δ-氨基乙酰丙酸脱水酶活性(ALA-D)、血浆中δ-氨基乙酰丙酸(ALA-P)、尿中δ-氨基乙酰丙酸(ALA-U)、尿中粪卟啉(CP-U)、红细胞原卟啉(EP)或锌原卟啉(ZP)、嘧啶5'-核苷酸酶(P5N)以及血液中的嘧啶核苷酸(PN)。采用CEC法或恢复法时,ALA-D的血铅阈值为5微克/分升。在血铅水平5至50微克/分升的较宽范围内,其有效性较高(>1.8),而CEC法测定的ALA-D活性在血铅水平20至50微克/分升时有效性较高。ALA-P的血铅阈值也低至5微克/分升,采用HPLC法或比色法时,ALA-U(校正肌酐后)的阈值分别在15至30微克/分升或20至40微克/分升之间。血铅水平为30和60微克/分升时,ALA-P的有效性较高(>1.8),而ALA-U仅在血铅水平为60微克/分升时有效性较高。血铅水平高于20至30微克/分升和40微克/分升时,EP(ZP)和CP-U分别显著升高。P5N活性的血铅阈值低于10微克/分升,血铅水平在10至60微克/分升之间时,其活性随血铅值升高呈线性下降。在血铅值超过40微克/分升时,所检测的生化参数中P5N的有效性最高(截断值<10微摩尔/小时/克血红蛋白时为1.86)。血铅水平高于60微克/分升时,PN升高。ALA-U、CP-U和ZP的个体差异相对大于PN。ALA-P似乎是铅暴露最理想的生物标志物之一,因为其分析方法简便、灵敏且特异,适用的血铅范围广泛,从正常水平到中毒水平。PN可能对铅中毒具有诊断价值。通过上述一些特定生物标志物的联合使用,可以更准确地评估铅效应或中毒情况。

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