利用核磁共振光譜儀探討大鼠代謝特徵與全氟癸酸暴露之關聯

Abstract

介紹: 全氟癸酸(PFDA)屬於全氟和多氟碳化物(PFASs)，因其持久性和生物累積性，PFDA廣泛應用於工業和消費產品中。流行病學和毒理學研究表明，PFDA暴露與人類健康和生物的許多負面影響有關，如肝毒性、生殖毒性和發育毒性。然而，其毒性的分子效應仍不清楚。 材料和方法: 本研究旨在鑑定雄性 Sprague-Dawley 大鼠在暴露於 PFDA 後內源性代謝物的變化。以口胃管注射方式使18 隻大鼠持續暴露每公斤0、0.5 和 1 毫克的 PFDA劑量21 天。收集了肝臟、腎臟、心臟、肺臟、胰臟、睾丸和血清等樣本。樣本經過萃取和預處理，隨後進行高解析度核磁共振儀（NMR）分析。光譜收集後進行多變量和單變量分析，隨後進行數據解釋。 結果與討論: 我們的實驗中，控制組和暴露組的大鼠體重沒有顯著差異。與控制組相比，肝臟重量有顯著增加。偏最小平方判別分析(PLSDA)發現肝臟、腎臟、心臟、肺臟和胰臟在控制組和暴露組之間顯示出分離模式，睾丸和血清則未發現分離趨勢。大鼠肝臟、腎臟、心臟、肺臟、胰臟和血清中特定代謝物的變化表明 PFDA 暴露後代謝過程受到干擾。代謝途徑的改變闡明了 PFDA 引起多個器官的潛在毒性作用和可能機轉。 結論: 基於 NMR 的代謝體學方法揭示了 PFDA 處理後大鼠多個器官和血清中代謝物的變化。儘管本研究 PFDA 暴露引起的代謝反應較輕微，但仍能從代謝物改變觀察到大鼠肝臟、腎臟、心臟、肺臟和胰臟為標的器官與其可能的毒性機轉。受影響代謝物的生物機制可作為未來研究 PFASs 毒性作用的方向。

Introduction: Perfluorodecanoic acid (PFDA) is one of the per- and polyfluoroalkyl substances. PFDA is widely used in industrial and consumer products due to its persistence and bioaccumulation. Epidemiology and toxicology studies showed PFDA exposure related to many negative effects on human health and organisms, such as liver toxicity, reproductive toxicity, and developmental toxicity. However, the possible toxic mechanisms are still unclear. Materials and methods: The study aims to identify changes in critical endogenous metabolites in male Sprague-Dawley rats after PFDA exposure. Eighteen rats were treated with PFDA at doses of 0, 0.5, and 1 mg/kg body weight/day via oral gavage for 21 days. Liver, kidney, heart, lung, pancreas, testis, and serum samples were collected. Samples were extracted and pretreated, followed by high-resolution nuclear magnetic resonance spectroscopy (NMR) analysis. Multivariate and univariate analysis were conducted after spectral collection, followed by data interpretation. Results and discussions: In our study, rat weights have no significant differences between the control group and the treated group. The liver weights have substantial increase in the high dose group compared with the control group. Partial least squares discriminant analysis (PLSDA) found that liver, kidney, heart, lung, and pancreas showed patterns of separation between control and treated groups except the testis and serum. Metabolic profiles in the liver, kidney, heart, lung, pancreas, and serum of rats suggested disrupted metabolic processes and related adverse effects after PFDA exposure. The altered metabolic pathways elucidate PFDA-induced potential toxic effects and possible mechanisms in multiple organs. Conclusion: The NMR-based metabolomics reveals the changes of metabolites in multiple organs and serum treated by PFDA in rats. Despite the subtle metabolic responses induced by PFDA exposure, we identified the target organs: liver, kidney, heart, lung, and pancreas, and their possible toxic effects. These potential toxic metabolisms may suggest direction for future research on PFAS toxicity.