Effects of Short and Long Exposure to Food Additive Titanium Dioxide (E171) in H9c2 Rat Cardiomyoblasts and in the Hearts of Rats.

Titanium dioxide (E171) is utilized in the food industry more frequently than other food additives because of its superior properties as a white colorant. Numerous in vitro studies have shown that E171 exhibits toxic effects on various cell types after a limited period of exposure. Previous observations indicate that E171 penetrates the cytoplasm of rat heart H9c2 myoblasts, leading to cell destruction after two days of treatment and impairing cardiac performance ex vivo within 10 min. Humans consume products containing E171 for extended periods; therefore, H9c2 cells were exposed to E171 once (short exposure) or multiple times (long exposure), and its toxic effects were examined after 5 weeks. Transmission electron microscopy (TEM) was used to analyze morphology and internalization. Cell counts were assessed, and cell death was evaluated using annexin plus propidium iodide (PI) and TUNEL assay. On the other hand, rats were orally administered E171 either once (acute exposure) or multiple times every other day over three months (chronic exposure), and the heart biomechanics were evaluated in a Langendorff system, as well as the infarct size by triphenyltetrazolium chloride staining. Experiments on H9c2 cells indicated that a single exposure to E171 (short) induced its absorption, a decrease in the cell number, and death after one week of exposure, and all these events were reversed after 5 weeks. Long exposure to E171 led to its internalization, inhibition of cell proliferation, alterations in cell morphology, and increased mortality during all weeks of treatment. Acute administration of E171 to rats did not induce alterations in cardiac function; however, chronic administration led to dysfunction, as indicated by a reduction in pressure and contractility index. The findings indicate that H9c2 cells and rodent hearts can recover after a brief E171 exposure, while prolonged exposure leads to substantial toxicity in both cardiac cells and cardiac tissue. Therefore, prolonged exposure to E171 could be potentially toxic to humans and lead to the development of cardiac dysfunctions.