Abstract：
Hexavalent chromium and its compounds are prevalent pollutants, especially in the work environment, pose a significant risk for multisystem toxicity and cancers. While it is known that chromium accumulation in the liver can cause damage, the dose-response relationship between blood chromium (Cr) and liver injury, as well as the possible potential toxic mechanisms involved, remains poorly understood. To address this, we conducted a follow-up study of 590 visits from 305 participants to investigate the associations of blood Cr with biomarkers for liver injury, including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL), and to evaluate the mediating effects of systemic inflammation. Platelet (PLT) and the platelet-to-lymphocyte ratio (PLR) were utilized as biomarkers of systemic inflammation. In the linear mixed-effects analyses, each 1-unit increase in blood Cr level was associated with estimated effect percentage increases of 0.82% (0.11%, 1.53%) in TBIL, 1.67% (0.06%, 3.28%) in DBIL, 0.73% (0.04%, 1.43%) in ALT and 2.08% (0.29%, 3.87%) in AST, respectively. Furthermore, PLT mediated 10.04%, 11.35%, and 10.77% increases in TBIL, DBIL, and ALT levels induced by chromate, respectively. In addition, PLR mediated 8.26% and 15.58% of the association between blood Cr and TBIL or ALT. These findings shed light on the mechanisms underlying blood Cr-induced liver injury, which is partly due to worsening systemic inflammation.
摘要：
六价铬及其化合物是普遍存在的污染物，尤其是在工作环境中，对多系统毒性和癌症构成重大风险。虽然已知铬在肝脏中的积累会引起损伤，血铬(Cr)与肝损伤的量效关系,以及可能涉及的潜在毒性机制，仍然知之甚少。为了解决这个问题，我们对来自305名参与者的590次访视进行了随访研究，以调查血液Cr与肝损伤的生物标志物的关联。包括血清丙氨酸氨基转移酶（ALT），天冬氨酸转氨酶（AST），总胆红素（TBIL），和直接胆红素（DBIL），并评估全身炎症的中介作用。血小板（PLT）和血小板淋巴细胞比率（PLR）被用作全身性炎症的生物标志物。在线性混合效应分析中，血Cr水平每增加1个单位，估计效应百分比增加0.82%(0.11%，1.53%)在TBIL中，1.67%（0.06%，3.28%)在DBIL中，0.73%（0.04%，1.43%)的ALT和2.08%(0.29%，3.87%)在AST中，分别。此外，PLT介导10.04%,11.35%,TBIL增加10.77%，DBIL,和铬酸盐诱导的ALT水平，分别。此外,PLR介导了8.26%和15.58%的血Cr与TBIL或ALT之间的关联。这些发现揭示了血液Cr诱导的肝损伤的潜在机制，部分原因是全身炎症恶化。
