RESUMO
BACKGROUND: Food-grade titanium dioxide (E171), a white colourant widely used in ultra-processed food products, has been banned in the European Union. However, its usage is still permitted in medicines, and in several other countries. The estimated intake of E171 in children is higher than in adults, which led us to hypothesise that E171 induces differential effects depending on age, with adult mice being the most susceptible due to age, despite the lower dose. AIM: To evaluate the effects of oral administration of E171 on intestinal permeability, ileum, and colon histology, and how these effects impact anxious and depressive behaviour in young and adult mice of both sexes. METHODS: Young and adult mice of both sexes C57BL/6 mice received 10 mg/kgbw E171/3 times per week for 3 months. E171 was administered orally in water by pipetting, while control groups only received drinking water, then intestinal permeability, histology and animal behaviour were analysed. RESULTS: E171 showed an amorphous shape, primary particles sized below 1 µm and anatase crystalline structure. Oral administration of E171 disrupted the intestinal permeability in adult male and female mice, but no effects were observed in young mice of both sexes. E171 promoted ileal adenoma formation in half of the adult female population, moreover hyperplastic crypts, and hyperplastic goblet cells at histological level in adult mice of both sexes. The colon presented hyperplastic goblet cells, hyperchromatic nuclei, increased proliferation and DNA damage in adult mice of both sexes. The anxiety and depressive behaviour were only altered in adult mice treated with E171, but no changes were detected in young animals of both sexes. CONCLUSIONS: Adult mice displayed higher susceptibility in all parameters analysed in this study compared to young mice of both sexes.
Assuntos
Aditivos Alimentares , Nanopartículas , Humanos , Criança , Masculino , Feminino , Animais , Camundongos , Aditivos Alimentares/química , Aditivos Alimentares/farmacologia , Camundongos Endogâmicos C57BL , Alimentos , Intestinos , Titânio/química , Nanopartículas/químicaRESUMO
Titanium dioxide is a food additive commonly used as a white food coloring (E171). Its wide use by the food industry associated with the nanometric size distribution of the particles of this pigment has shown high genotoxicity associated with recurrent exposure by ingestion. Therefore, the use of E171 in food products has already been banned by some industries and in the European Union. Such banishment should soon be extended to other countries around the world, making it important to establish techniques for the efficient determination of TiO2 in different food products. The association between hyperspectral images and chemometric tools can be useful in this sense, aiming to enable the use of a single method for sample preparation and analysis of different types of food. Thus, the present work aims to evaluate the use of Raman mapping associated with the resolution of multivariate curves with alternating least squares (MCR-ALS) for the determination of titanium dioxide in solid food samples with different compositions, without the need to introduce specific sample preparation. The proposed method allowed for the first-time quantification of TiO2 in different food matrices without specific sample preparation, with a simple, rapid, accurate (93% of recovery), low detection limits (0.0111% m/m) and quantification (0.0370% m/m) and adequate linearity (r = 0.9990) and precise (standard deviation around 0.020-0.030% w/w) methodology. Such results highlight the potential use of Raman mapping associated with the MCR-ALS for quantification of the nano-TiO2 in commercial samples.
Assuntos
Alimentos , Titânio , Análise dos Mínimos Quadrados , Titânio/análise , Aditivos Alimentares , Análise MultivariadaRESUMO
Titanium dioxide food grade (E171) is one of the most used food additives containing nanoparticles. Recently, the European Food Safety Authority indicated that E171 could no longer be considered safe as a food additive due to the possibility of it being genotoxic and there is evidence that E171 administration exacerbates colon tumor formation in murine models. However, less is known about the effects of E171 accumulation once the exposure stopped, then we hypothesized that toxic effects could be detected even after E171 removal. Therefore, we investigated the effects of E171 exposure after being removed from colon cell cultures. Human colon cancer cell line (HCT116) was exposed to 0, 1, 10 and 50 µg/cm2 of E171. Our results showed that in the absence of cytotoxicity, E171 was accumulated in the cells after 24 of exposure, increasing granularity and reactive oxygen species, inducing alterations in the molecular pattern of nucleic acids and lipids, and causing nuclei enlargement, DNA damage and tubulin depolymerization. After the removal of E171, colon cells were cultured for 48 h more hours to analyze the ability to restore the previously detected alterations. As we hypothesized, the removal of E171 was unable to revert the alterations found after 24 h of exposure in colon cells. In conclusion, exposure to E171 causes alterations that cannot be reverted after 48 h if E171 is removed from colon cells.
Assuntos
Nanopartículas , Titânio , Animais , Colo , Aditivos Alimentares/toxicidade , Humanos , Camundongos , Nanopartículas/toxicidade , Titânio/toxicidadeRESUMO
Cardiovascular diseases are the leading cause of death worldwide. Food-grade TiO2 (E171) is the most widely used additive in the food industry. Existing evidence shows TiO2 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.
Assuntos
Nanopartículas , Titânio , Animais , Sobrevivência Celular , Aditivos Alimentares/toxicidade , Nanopartículas/toxicidade , Ratos , Titânio/toxicidadeRESUMO
Colorectal cancer is the fourth worldwide cause of death and even if some dietary habits are consider risk factors, the contribution of food additives including foodgrade titanium dioxide (TiO2), designated as E171, has been poorly investigated. We hypothesized that oral E171 intake could have impact on the enhancement of colorectal tumor formation and we aimed to investigate if E171 administration could enhance tumor formation in a colitis associated cancer (CAC) model. BALB/c male mice were grouped as follows: a) control, b) E171, c) CAC and d) CAC + E171 group (n = 6). E171 used in this study formed agglomerates of 300 nm in water. E171 intragastric administration (5 mg/kg body weight/5 days/10 weeks) was unable to induce tumor formation but dysplastic alterations were observed in the distal colon but enhanced the tumor formation in distal colon (CAC + E171 group) measured by tumor progression markers. Some E171 particles were internalized in colonic cells of the E171 and CAC + E171 groups and both groups showed a decrease in goblet cells in the distal colon. However the CAC + E171 group showed a higher decrease of these cells that act as protection barrier in colon. These results suggest that E171 could worsen pre-existent intestinal diseases.