Food-grade titanium dioxide (E171) and zinc oxide nanoparticles induce mitochondrial permeability and cardiac damage after oral exposure in rats

Abstract

Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are found in diverse products for human use. E171 is used as whitening agent in food and cosmetics, and ZnO NPs in food packaging. Their potential multi-organ toxicity has raised concerns on their safety. Since mitochondrial dysfunction is a key aspect of cardio-pathologies, here, we evaluate the effect of chronic exposure to E171 and ZnO NPs in rats on cardiac mitochondria. Changes in cardiac electrophysiology and body weight were measured. E171 reduced body weight more than 10% after 5 weeks. Both E171 and ZnO NPs increased systolic blood pressure (SBP) from 110–120 to 120–140 mmHg after 45 days of treatment. Both NPs altered the mitochondrial permeability transition pore (mPTP), reducing calcium requirement for permeability by 60% and 93% in E171- and ZnO NPs-exposed rats, respectively. Treatments also affected conformational state of adenine nucleotide translocase (ANT). E171 reduced the binding of EMA to Cys 159 in 30% and ZnO NPs in 57%. Mitochondrial aconitase activity was reduced by roughly 50% with both NPs, indicating oxidative stress. Transmission electron microscopy (TEM) revealed changes in mitochondrial morphology including sarcomere discontinuity, edema, and hypertrophy in rats exposed to both NPs. In conclusion, chronic oral exposure to NPs induces functional and morphological damage in cardiac mitochondria, with ZnO NPs being more toxic than E171, possibly due to their dissociation in free Zn²⁺ ion form. Therefore, chronic intake of these food additives could increase risk of cardiovascular disease.

Keywords:

• E171
• titanium dioxide nanoparticles
• zinc oxide nanoparticles
• mitochondrial dysfunction
• cardiac damage

Acknowledgements

We thank technical support from Olga Lidia Pérez Reyes from Departamento de Patología, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, México, for processing cardiac tissue slides as well as HE and TRCM staining.

Author contributions

Francisco Correa Segura: methodology, research, and writing – review and editing; Fernanda Isabel Macías Macías: methodology; Kimberly Abigaíl Velázquez Delgado: methodology; María del Pilar Ramos-Godinez: research, analysis, roles/writing – original draft; Angélica Ruiz-Ramírez: research; Pedro Flores: methodology, research, analysis, roles/writing – original draft; Elizabeth Huerta-García: software, writing – review and editing; Rebeca López-Marure: conceptualization, validation, resources, visualization, supervision, roles/writing – original draft, writing – review and editing, project administration, funding acquisition.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm data supporting findings of this study are available within the article [and/or] supplementary materials.