Metallic nanoparticles (NPs) are widely used as food additives for human consumption. NPs reach the bloodstream given their small size, getting in contact with all body organs and cells. NPs have adverse effects on the respiratory and intestinal tract; however, few studies have focused on the toxic consequences of orally ingested metallic NPs on the cardiovascular system. Here, the effects of two food-grade additives on the cardiovascular system were analyzed. Titanium dioxide labeled as E171 and zinc oxide (ZnO) NPs were orally administered to Wistar rats using an esophageal cannula at 10 mg/kg bw every other day for 90 days. We evaluated cardiac cell morphology and death, expression of apoptotic and autophagic proteins in cardiac mitochondria, mitochondrial dysfunction, and concentration of metals on cardiac tissue. Heart histology showed important morphological changes such as presence of cellular infiltrates, collagen deposition and mitochondrial alterations in hearts from rats exposed to E171 and ZnO NPs. Intracellular Cyt-C levels dropped, while TUNEL positive cells increased. No significant changes in the expression of inflammatory cytokines were detected. Both NPs altered mitochondrial function indicating cardiac dysfunction, which was associated with an elevated concentration of calcium. ZnO NPs induced expression of caspases 3 and 9 and two autophagic proteins, LC3B and beclin-1, and had the strongest effect compared to E171. E171 and ZnO NPs induce adverse cardiovascular effects in rats after 90 days of exposure, thus food intake containing these additives, should be taken into consideration, since they translocate into the bloodstream and cause cardiovascular damage.

中文翻译：

---

食品级二氧化钛和氧化锌纳米颗粒在大鼠口服暴露后会引起毒性和心脏损伤

金属纳米粒子（NP）广泛用作人类消费的食品添加剂。由于纳米粒子体积小，因此可以到达血液，与所有身体器官和细胞接触。NPs对呼吸道和肠道有不良影响；然而，很少有研究关注口服金属纳米粒子对心血管系统的毒性后果。这里分析了两种食品级添加剂对心血管系统的影响。使用食管插管，每隔一天向 Wistar 大鼠口服标记为 E171 的二氧化钛和氧化锌 (ZnO) NP，剂量为 10 mg/kg 体重，持续 90 天。我们评估了心脏细胞形态和死亡、心脏线粒体中凋亡和自噬蛋白的表达、线粒体功能障碍以及心脏组织中的金属浓度。心脏组织学显示暴露于 E171 和 ZnO NP 的大鼠心脏中存在重要的形态学变化，例如细胞浸润、胶原蛋白沉积和线粒体改变。细胞内 Cyt-C 水平下降，而 TUNEL 阳性细胞增加。未检测到炎症细胞因子表达的显着变化。两种纳米颗粒都改变了线粒体功能，表明心脏功能障碍，这与钙浓度升高有关。ZnO NPs 诱导 caspase 3 和 9 以及两种自噬蛋白 LC3B 和 beclin-1 的表达，并且与 E171 相比效果最强。E171 和 ZnO NPs 暴露 90 天后会对大鼠产生不良心血管影响，因此应考虑含有这些添加剂的食物摄入，因为它们会转移到血液中并导致心血管损伤。