Departamento de Fisiología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Departamento de Microscopía Electrónica, Instituto Nacional de Cancerología, Mexico City, Mexico.
Cardiovasc Toxicol. 2022 Aug;22(8):713-726. doi: 10.1007/s12012-022-09747-5. Epub 2022 May 28.
Cardiovascular diseases are the leading cause of death worldwide. Food-grade TiO (E171) is the most widely used additive in the food industry. Existing evidence shows TiO nanoparticles reach systemic circulation through biological barriers, penetrate cell membranes, accumulate in cells of different organs, and cause damage; however, their effects on cardiac cells and the development of heart diseases are still unexplored. Therefore, in this work, we tested E171 toxicity in rat cardiomyoblasts and hearts. E171 internalization and impact on cell viability, proliferation, mitochondria, lysosomes, F-actin distribution, and cell morphology were evaluated in H9c2 cells. Additionally, effects of E171 were measured on cardiac function in ex vivo rat hearts. E171 was uptaken by cells and translocated into the cytoplasm. E171 particles changed cell morphology reducing proliferation and metabolic activity. Higher caspase-3 and caspase-9 expression as well as Tunel-positive cells induced by E171 exposure indicate apoptotic death. Mitochondrial and lysosome alterations resulting from mitophagy were detected after 24 and 48 h exposure, respectively. Additionally, high E171 concentrations caused rearrangements of the F-actin cytoskeleton. Finally, hearts exposed to E171 showed impaired cardiac function. These results support E171 toxicity in cardiac cells in vitro altering cardiac function in an ex vivo model, indicating that consumption of this food additive could be toxic and may lead to the development of cardiovascular disease.
心血管疾病是全球范围内的主要死因。食品级 TiO（E171）是食品工业中使用最广泛的添加剂。现有证据表明，TiO 纳米颗粒通过生物屏障进入全身循环，穿透细胞膜，在不同器官的细胞中积累，并造成损伤；然而，它们对心肌细胞和心脏病发展的影响仍未得到探索。因此，在这项工作中，我们测试了 E171 在大鼠心肌细胞和心脏中的毒性。在 H9c2 细胞中评估了 E171 的内化及其对细胞活力、增殖、线粒体、溶酶体、F-肌动蛋白分布和细胞形态的影响。此外，还测量了 E171 对离体大鼠心脏心功能的影响。E171 被细胞摄取并转移到细胞质中。E171 颗粒改变细胞形态，降低增殖和代谢活性。E171 暴露诱导的 caspase-3 和 caspase-9 表达增加以及 Tunel 阳性细胞表明凋亡死亡。暴露 24 和 48 小时后分别检测到线粒体和溶酶体因自噬而发生改变。此外，高浓度的 E171 会引起 F-肌动蛋白细胞骨架的重排。最后，暴露于 E171 的心脏表现出心脏功能受损。这些结果支持 E171 在体外心肌细胞中的毒性，改变了离体模型中的心脏功能，表明这种食品添加剂的消耗可能具有毒性，并可能导致心血管疾病的发展。
