Stopforth Cameron K, Sears Clara, Gao Hong, Riggs Daniel W, Srivastava Shweta, Krivokhizhina Tatiana, Hart Joy L, Walker Kandi L, Srivastava Sanjay, Bhatnagar Aruni, Keith Rachel J
Christina Lee Brown Envirome Institute, School of Medicine, University of Louisville, 302 E Muhammad Ali Blvd, Louisville, KY, 40202, USA; Department of Physiology, School of Medicine, University of Louisville, 500 S. Preston St, Louisville, KY, 40202, USA.
Christina Lee Brown Envirome Institute, School of Medicine, University of Louisville, 302 E Muhammad Ali Blvd, Louisville, KY, 40202, USA; Department of Medicine, School of Medicine, University of Louisville, 550 S. Jackson St, Louisville, KY, 40202, USA.
Environ Res. 2025 Jul 25;285(Pt 2):122451. doi: 10.1016/j.envres.2025.122451.
Volatile organic compounds (VOCs) are ubiquitous gaseous chemicals emitted from multiple sources and present in both indoor and outdoor air. VOC exposures have been linked to detrimental cardiometabolic effects; nevertheless, the underlying mechanisms remain unclear. In this study, we evaluated the relationship between VOC exposure and sympathetic activation.
Participants (n=696, age 25-70 years) were recruited between 2018 and 2021 in Louisville, KY. Clean catch, spot urine samples were obtained. Urinary metabolites of VOCs and monoamines were quantified using UPLC-MS/MS. The associations of creatinine-adjusted, log-transformed urinary constituents were examined using adjusted multivariable linear regression models for individual metabolites and quantile-based g-computation for overall mixture models. Final models were adjusted for demographics, stress, smoking status, medication use, and urine collection time.
Higher urinary levels of several VOC metabolites were associated with higher urinary levels of monoamines and their metabolites. A quartile increase in the overall VOC metabolite mixture was associated with 27% [18%, 37%] (serotonin) to 54% [36%, 73%] (epinephrine) higher urinary parent monoamine concentrations. For phase I monoamine metabolites, concentrations were 25% [16%, 35%] (vanillylmandelic acid) to 37% [29%, 46%] (3-methoxytyramine) higher per quartile increase in VOC metabolite mixture.
Our results suggest that exposure to VOCs is associated with elevated sympathetic activation. Individual and mixture analyses identified robust associations with metabolites of N,N-dimethylformamide, 1,3-butadiene, ethylbenzene/styrene, propylene oxide, and crotonaldehyde. Elevated sympathetic tone may be a significant contributor to the negative cardiometabolic outcomes associated with VOC exposure.
挥发性有机化合物(VOCs)是从多种来源排放的普遍存在的气态化学物质,存在于室内和室外空气中。接触VOCs与有害的心脏代谢效应有关;然而,其潜在机制仍不清楚。在本研究中,我们评估了VOC暴露与交感神经激活之间的关系。
2018年至2021年期间在肯塔基州路易斯维尔招募了参与者(n = 696,年龄25 - 70岁)。采集清洁中段尿样本。使用超高效液相色谱 - 串联质谱法(UPLC - MS/MS)对VOCs和单胺类物质的尿液代谢产物进行定量分析。对于单个代谢产物,使用调整后的多变量线性回归模型检查肌酐校正的、对数转换后的尿液成分之间的关联;对于整体混合物模型,使用基于分位数的g计算法。最终模型针对人口统计学特征、压力、吸烟状况、药物使用情况和尿液收集时间进行了调整。
几种VOC代谢产物的尿液水平升高与单胺类物质及其代谢产物的尿液水平升高有关。VOC代谢产物混合物总体增加一个四分位数与尿液中单胺母体浓度升高27%[18%,37%](血清素)至54%[36%,73%](肾上腺素)相关。对于I期单胺代谢产物,VOC代谢产物混合物每增加一个四分位数,浓度升高25%[16%,35%](香草扁桃酸)至37%[29%,46%](3 - 甲氧基酪胺)。
我们的结果表明,接触VOCs与交感神经激活增强有关。个体和混合物分析确定了与N,N - 二甲基甲酰胺、1,3 - 丁二烯、乙苯/苯乙烯、环氧丙烷和巴豆醛的代谢产物之间存在显著关联。交感神经张力升高可能是与VOC暴露相关的负面心脏代谢结果的一个重要因素。