Department of Chemistry, New Mexico Institute of Mining and Technology, Socorro, NM, 87801, USA.
Department of Biology, New Mexico Institute of Mining and Technology, Socorro, NM, 87801, USA.
Ecotoxicol Environ Saf. 2020 Jan 30;188:109892. doi: 10.1016/j.ecoenv.2019.109892. Epub 2019 Nov 12.
Increasing quantities of pharmaceutical waste in the environment have disrupted the balance of ecosystems, and may have subsequent effects on human health. Although a handful of previous studies have shown the impacts of pharmaceutically active compounds on the environment, the toxicological effects of their degradation products remain largely unknown. In the current study, the photo-degradation products of environmental ibuprofen were assessed for both ecotoxicological and human health effects using a series of in vitro assays. Here, six of the major degradation products are synthesized with high purity (>98%) and characterized with HNMR, CNMR, FT-IR and HRMS. To evaluate human health effects, three gut microbiota species, Lactobacillus acidophilus, Enterococcus faecalis and Escherichia coli, and two human cell lines, HEK293T and HepG2, are exposed to various concentrations of ibuprofen and its degradation products. On L. acidophilus, the ibuprofen degradation product (±)-(2R,3R)-2-(4-isobutylphenyl)-5-methylhexan-3-ol shows a greater toxic effect while ibuprofen enhances its growth at lower concentrations. At higher concentrations, ibuprofen shows at least a 2-fold higher toxicity compared to that of its degradation products. However, E. faecalis shows little or no effect upon exposure to these compounds. An induction of the SOS response in E. coli is observed but limited to only ibuprofen and 4-acetylbenzoic acid. In human cell line studies, survival of both HEK293T and HepG2 cell lines is profoundly impaired by the photo-degradation products of (±)- (2R,3R)-2-(4-isobutylphenyl)-5-methylhexan-3-ol, (±)-(2R,3S)-2-(4-isobutylphenyl)-5-methylhexan-3-ol, and (±)-1-(4-(1-hydroxy-2methylpropyl)phenyl)ethan-1-one. In this work, the bioluminescence bacterium, Aliivibrio fischeri, is used as a model to assess environmental impact. Both ibuprofen and its degradation products inhibit the growth of this gram-negative bacteria with the primary compound showing the most significant impact. Overall, our results highlight that some of the degradation products of ibuprofen can be more toxic to human kidney cell line and liver cell line than the parent compound while ibuprofen can be more toxic to human gut microbiota and A. fischeri than ibuprofen degradation products.
越来越多的药物废物进入环境，破坏了生态系统的平衡，并可能对人类健康产生后续影响。尽管之前有一些研究表明，药用活性化合物对环境有影响，但它们的降解产物的毒理学效应在很大程度上仍不清楚。在本研究中，使用一系列体外测定法评估了环境布洛芬的光降解产物对生态毒理学和人类健康的影响。在这里，用高纯度（>98%）合成了六种主要的降解产物，并通过 HNMR、CNMR、FT-IR 和 HRMS 进行了表征。为了评估人类健康影响，将三种肠道微生物物种，嗜酸乳杆菌、粪肠球菌和大肠杆菌，以及两种人类细胞系，HEK293T 和 HepG2，暴露于不同浓度的布洛芬及其降解产物中。在嗜酸乳杆菌中，布洛芬降解产物（±）-（2R，3R）-2-（4-异丁基苯基）-5-甲基己烷-3-醇显示出更大的毒性作用，而布洛芬在较低浓度下促进其生长。在较高浓度下，布洛芬的毒性至少比其降解产物高 2 倍。然而，粪肠球菌暴露于这些化合物时几乎没有或没有影响。在大肠杆菌中观察到 SOS 反应的诱导，但仅限于布洛芬和 4-乙酰苯甲酸。在人类细胞系研究中，（±）-（2R，3R）-2-（4-异丁基苯基）-5-甲基己烷-3-醇、（±）-（2R，3S）-2-（4-异丁基苯基）-5-甲基己烷-3-醇和（±）-1-（4-（1-羟基-2-甲基丙基）苯基）-1-酮的光降解产物严重损害了 HEK293T 和 HepG2 细胞系的存活。在这项工作中，发光细菌 Aliivibrio fischeri 被用作模型来评估环境影响。布洛芬及其降解产物都抑制了这种革兰氏阴性菌的生长，主要化合物的影响最大。总的来说，我们的结果表明，布洛芬的一些降解产物对人类肾细胞系和肝细胞系的毒性可能比母体化合物更大，而布洛芬对人类肠道微生物群和 A 的毒性比布洛芬降解产物更大。 Fischeri。
