Department of Public Health, Section of Environmental Health, Faculty of Health and Medical Sciences, University of Copenhagen, Øster Farimagsgade 5A, Building 5B, 2nd Floor, DK-1014, Copenhagen K, Denmark.
Department of Drug Design and Pharmacology, Section of Molecular and Cellular Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 22, 2100, Copenhagen, Denmark.
Part Fibre Toxicol. 2018 Feb 26;15(1):12. doi: 10.1186/s12989-018-0248-2.
Humans are continuously exposed to particles in the gastrointestinal tract. Exposure may occur directly through ingestion of particles via food or indirectly by removal of inhaled material from the airways by the mucociliary clearance system. We examined the effects of food-grade particle exposure on vasomotor function and systemic oxidative stress in an ex vivo study and intragastrically exposed rats.
In an ex vivo study, aorta rings from naïve Sprague-Dawley rats were exposed for 30 min to food-grade TiO (E171), benchmark TiO (Aeroxide P25), food-grade vegetable carbon (E153) or benchmark carbon black (Printex 90). Subsequently, the vasomotor function was assessed in wire myographs. In an in vivo study, lean Zucker rats were exposed intragastrically once a week for 10 weeks to vehicle, E171 or E153. Doses were comparable to human daily intake. Vasomotor function in the coronary arteries and aorta was assessed using wire myographs. Tetrahydrobiopterin, ascorbate, malondialdehyde and asymmetric dimethylarginine were measured in blood as markers of oxidative stress and vascular function.
Direct exposure of E171 to aorta rings ex vivo increased the acetylcholine-induced vasorelaxation and 5-hydroxytryptamine-induced vasocontraction. E153 only increased acetylcholine-induced vasorelaxation, and Printex 90 increased the 5-hydroxytryptamine-induced vasocontraction, whereas Aeroxide P25 did not affect the vasomotor function. In vivo exposure showed similar results as ex vivo exposure; increased acetylcholine-induced vasorelaxation in coronary artery segments of E153 and E171 exposed rats, whereas E171 exposure altered 5-hydroxytryptamine-induced vasocontraction in distal coronary artery segments. Plasma levels of markers of oxidative stress and vascular function showed no differences between groups.
Gastrointestinal tract exposure to E171 and E153 was associated with modest albeit statistically significant alterations in the vasocontraction and vasorelaxation responses. Direct particle exposure to aorta rings elicited a similar type of response. The vasomotor responses were not related to biomarkers of systemic oxidative stress.
人类持续暴露于胃肠道中的颗粒。暴露可能直接通过食物摄入颗粒而发生，也可能间接通过黏膜纤毛清除系统从气道中清除吸入的物质而发生。我们在离体研究和胃内暴露的大鼠中研究了食物级颗粒暴露对血管舒缩功能和全身氧化应激的影响。
在离体研究中，将 naive Sprague-Dawley 大鼠的主动脉环暴露于食物级 TiO（E171）、基准 TiO（Aeroxide P25）、食物级植物碳（E153）或基准炭黑（Printex 90）30 分钟。随后，在 wire myographs 中评估血管舒缩功能。在体内研究中，瘦型 Zucker 大鼠每周经胃内暴露一次，持续 10 周，分别给予载体、E171 或 E153。剂量与人类每日摄入量相当。使用 wire myographs 评估冠状动脉和主动脉的血管舒缩功能。在血液中测量四氢生物蝶呤、抗坏血酸、丙二醛和非对称二甲基精氨酸作为氧化应激和血管功能的标志物。
E171 直接暴露于离体主动脉环增加了乙酰胆碱诱导的血管舒张和 5-羟色胺诱导的血管收缩。E153 仅增加了乙酰胆碱诱导的血管舒张，而 Printex 90 增加了 5-羟色胺诱导的血管收缩，而 Aeroxide P25 则不影响血管舒缩功能。体内暴露显示与离体暴露相似的结果；E153 和 E171 暴露的大鼠冠状动脉段中乙酰胆碱诱导的血管舒张增加，而 E171 暴露改变了远端冠状动脉段中 5-羟色胺诱导的血管收缩。各组之间的氧化应激和血管功能标志物的血浆水平没有差异。
胃肠道暴露于 E171 和 E153 与血管收缩和舒张反应的适度但具有统计学意义的改变有关。主动脉环的直接颗粒暴露引起了类似的反应。血管舒缩反应与系统氧化应激的生物标志物无关。
