Food Additive Titanium Dioxide (E171) Increases Intracellular Labile Fe2+ Levels and Induces Oxidative Stress and Mitochondrial Dysfunction in H9c2 Cardiomyoblasts.

Abstract

Food-grade titanium dioxide (E171) is widely used as a food additive and has raised concerns about its potential systemic toxicity. However, its impact on cardiac cellular metabolism and mitochondrial function remains incompletely understood. In the present study, we investigated the effects of E171 on intracellular labile iron, oxidative stress, mitochondrial ultrastructure, and mitochondrial bioenergetics in H9c2 cardiomyoblasts. Exposure to E171 leads to a significant increase in intracellular labile iron (Fe²⁺) levels. This alteration was accompanied by elevated reactive oxygen species (ROS) production and reduced intracellular glutathione levels, consistent with enhanced oxidative stress following E171 exposure. Ultrastructural analysis by transmission electron microscopy (TEM) revealed marked mitochondrial alterations, including reduced cristae density and structural damage. Functional assessment of mitochondrial bioenergetics demonstrated impaired oxidative phosphorylation and reduced maximal respiratory capacity in E171-treated cells. The potential protective role of quercetin (a powerful antioxidant and iron chelator) was explored in mitochondrial respiration assays; however, at the concentration and exposure conditions tested, quercetin treatment did not fully restore the bioenergetic parameters induced by E171. Collectively, these findings indicate that E171 increases intracellular labile iron levels and promotes oxidative stress, associated with alterations in mitochondrial ultrastructure and impaired bioenergetic function in H9c2 cardiomyoblasts, suggesting a potential mechanism by which food additives may affect cardiac cellular metabolism.