Institute of Environment and Ecology, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
State Environmental Protection Key Lahoratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China.
Ecotoxicol Environ Saf. 2024 Sep 1;282:116708. doi: 10.1016/j.ecoenv.2024.116708. Epub 2024 Jul 16.
Previous studies reported that hemoprotein CYP450 catalyzed triclosan coupling is an "uncommon" metabolic pathway that may enhance toxicity, raising concerns about its environmental and health impacts. Hemoglobin, a notable hemoprotein, can catalyze endogenous phenolic amino acid tyrosine coupling reactions. Our study explored the feasibility of these coupling reactions for exogenous phenolic pollutants in plasma. Both hemoglobin and hemin were found to catalyze triclosan coupling in the presence of H₂O₂. This resulted in the formation of five diTCS-2 H, two diTCS-Cl-3 H, and twelve triTCS-4 H in phosphate buffer, with a total of nineteen triclosan coupling products monitored using LC-QTOF. In plasma, five diTCS-2 H, two diTCS-Cl-3 H, and two triTCS-4 H were detected in hemoglobin-catalyzed reactions. Hemin showed a weaker catalytic effect on triclosan transformation compared to hemoglobin, likely due to hemin dimerization and oxidative degradation by H₂O₂, which limits its catalytic efficiency. Triclosan transformation in the human plasma-like medium still occurs with high H₂O₂, despite the presence of antioxidant proteins that typically inhibit such transformations. In plasma, free H₂O₂ was depleted within 40 minutes when 800 µM H₂O₂ was added, suggesting a rapid consumption of H₂O₂ in these reactions. Antioxidative species, or hemoglobin/hemin scavengers such as bovine serum albumin, may inhibit but not completely terminate the triclosan coupling reactions. Previous studies reported that diTCS-2 H showed higher hydrophobicity and greater endocrine-disrupting effects compared to triclosan, which further underscores the potential health risks. This study indicates that hemoglobin and heme in human plasma might significantly contribute to phenolic coupling reactions, potentially increasing health risks.
先前的研究报告称，血红素细胞色素 P450 催化的三氯生偶联是一种“罕见”的代谢途径，可能会增强其毒性，引发了人们对其环境和健康影响的担忧。血红蛋白作为一种重要的血红素蛋白，可以催化内源性酚基氨基酸酪氨酸的偶联反应。本研究探索了这些偶联反应在血浆中外源酚类污染物的可行性。研究发现，在 H₂O₂存在的情况下，血红蛋白和血红素均可催化三氯生偶联。这导致在磷酸盐缓冲液中形成了五个二氯三氯乙酰胺-2- 氢（diTCS-2 H）、两个二氯三氯乙酰胺-Cl-3- 氢（diTCS-Cl-3 H）和十二个三氯三氯乙酰胺-4- 氢（triTCS-4 H），共监测到十九种三氯生偶联产物。在血红蛋白催化的反应中，血浆中检测到五个二氯三氯乙酰胺-2- 氢（diTCS-2 H）、两个二氯三氯乙酰胺-Cl-3- 氢（diTCS-Cl-3 H）和两个三氯三氯乙酰胺-4- 氢（triTCS-4 H）。与血红蛋白相比，血红素对三氯生转化的催化作用较弱，这可能是由于血红素二聚化和 H₂O₂的氧化降解，限制了其催化效率。尽管存在通常抑制此类转化的抗氧化蛋白，但在高浓度 H₂O₂存在的人血浆样介质中，三氯生仍会发生转化。在添加 800 µM H₂O₂时，血浆中 40 分钟内耗尽了游离 H₂O₂，表明这些反应中 H₂O₂的消耗速度很快。抗氧化物质或血红蛋白/血红素清除剂（如牛血清白蛋白）可能会抑制但不能完全终止三氯生偶联反应。先前的研究报告称，与三氯生相比，二氯三氯乙酰胺-2- 氢（diTCS-2 H）显示出更高的疏水性和更大的内分泌干扰作用，这进一步强调了潜在的健康风险。本研究表明，人血浆中的血红蛋白和血红素可能会显著促进酚类偶联反应，从而增加健康风险。
