Ecotoxicology and Environmental Safety ( IF 6.2 ) Pub Date : 2021-12-27 , DOI: 10.1016/j.ecoenv.2021.113124 Yuan Wang 1 , Mengbei Qin 1 , Xiao Wang 1 , Junling Han 1 , Ruidun Chen 2 , Min Zhang 1 , Wei Gu 1
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Objective
Parabens are commonly used as preservatives in foodstuffs, cosmetics, and pharmaceutical products. The widespread use of parabens has led to their leaking into the environment. Concerns about the safety of parabens have recently increased due to their potential endocrine–disrupting effects as an emerging contaminant. Thus, it is necessary to study the metabolism of parabens in vivo.
Methods
In this study, Drosophila melanogaster in males and females were exposed to ethylparaben (EP) concentration group (300 mg/L, 700 mg/L, and 1000 mg/L), and control group (0 mg/L) by the capillary feeding assay (CAFE). We quantified the activity of the detoxification-related carboxylesterase (CarE). The contents of EP metabolites in D. melanogaster, including p-hydroxybenzoic acid (PHBA), methylparaben (MP), and intact EP were carried out by high-performance liquid chromatography (HPLC). The regression model between EP metabolites (PHBA and MP) and CarE was developed using the Fourier series fitting method.
Results
The general level of EP metabolites (PHBA, MP, and intact EP) accumulation was accounted for 5.6−11.5% in D. melanogaster. As EP accumulated, the activity of CarE increased, and the activity of CarE in females was higher than males, which is inconsistent with the result of EP intake dose. Additionally, there were significant differences in the proportion of EP metabolites between female and male flies, and the results of sex comparison were different depending on the EP treated groups and EP metabolites. In general, PHBA of EP hydrolytic product and MP of EP transesterification product in D. melanogaster were 41.4−63.9% and 10.4−24.6%, respectively. In terms of the rest of the EP existed in intact form and ranged from 22.4% to 34.0%. Moreover, the EP metabolites in the conjugated form were higher than those in the free form. The regression model between EP metabolites and CarE was established, showing that the CarE activity can be used to estimate the content of PHBA and MP.
Conclusion
The result indicates that the EP can accumulate in the body through food. Hydrolysis is the main metabolic pathway of EP in D. melanogaster, and transesterification is another metabolic pathway of EP. Additionally, the EP metabolites in flies mainly exist in conjugated form. Furthermore, the Fourier series fitting method model between EP metabolites and CarE, providing theoretical support to study the dose–effect relationship between metabolites of parabens and CarE. This study not only provides a mathematical basis for the safety evaluation of parabens, but also provides support for the further study of the toxicological effects of parabens.
中文翻译：
尼泊金乙酯在果蝇体内的残留行为及代谢途径
客观的
对羟基苯甲酸酯通常用作食品、化妆品和药品中的防腐剂。对羟基苯甲酸酯的广泛使用导致其泄漏到环境中。由于对羟基苯甲酸酯作为一种新兴污染物具有潜在的内分泌干扰作用，最近人们对其安全性的担忧有所增加。因此，有必要研究对羟基苯甲酸酯在体内的代谢。
方法
在本研究中，雄性和雌性果蝇通过毛细管喂养暴露于尼泊金乙酯（EP）浓度组（300 mg/L、700 mg/L和1000 mg/L）和对照组（0 mg/L）。测定（CAFE）。我们量化了解毒相关的羧酸酯酶（CarE）的活性。采用高效液相色谱法（HPLC）测定黑腹果蝇中EP代谢物对羟基苯甲酸（PHBA）、对羟基苯甲酸甲酯（MP）和完整EP的含量。使用傅立叶级数拟合方法建立了 EP 代谢物（PHBA 和 MP）与 CarE 之间的回归模型。
结果
黑腹果蝇中 EP 代谢物（PHBA、MP 和完整 EP）积累的一般水平占 5.6−11.5% 。随着EP的积累，CarE活性增加，且女性CarE活性高于男性，这与EP摄入剂量的结果不一致。此外，雌性和雄性果蝇之间EP代谢物的比例存在显着差异，并且性别比较的结果根据EP处理组和EP代谢物的不同而不同。总体而言，黑腹果蝇EP水解产物的PHBA和EP酯交换产物的MP分别为41.4−63.9%和10.4−24.6%。EP 的其余部分以完整形式存在，范围为 22.4% 至 34.0%。此外，缀合形式的EP代谢物高于游离形式。建立了EP代谢物与CarE之间的回归模型，表明CarE活性可以用来估计PHBA和MP的含量。
结论
结果表明EP可以通过食物在体内积累。水解是黑腹果蝇EP的主要代谢途径，酯交换是EP的另一代谢途径。此外，果蝇体内的EP代谢物主要以结合形式存在。此外，EP代谢物与CarE之间的傅里叶级数拟合方法模型，为研究对羟基苯甲酸酯类代谢物与CarE之间的量效关系提供了理论支持。该研究不仅为对羟基苯甲酸酯类药物的安全性评价提供了数学基础，也为进一步研究对羟基苯甲酸酯类药物的毒理作用提供了支撑。
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