Renal tubular response to titanium dioxide nanoparticles exposure

Abstract

Titatinum dioxide nanoparticles (TiO₂-NPs) are frequently used in several areas. Titanium alloys are employed in orthopedic and odontological surgery (such as hip, knee, and teeth implants). To evaluate the potential acute toxic effects of titanium pieces implantations and in other sources that allow the systemic delivery of titanium, parenteral routes of TiO₂-NPs administration should be taken into account. The present study evaluated the impact of subcutaneous administration of TiO₂-NPs on renal function and structure in rats. Animals were exposed to a dose of 50 mg/kg b.w., s.c. and sacrificed after 48 h. Titanium levels were detected in urine (135 ± 6 ηg/mL) and in renal tissue (502 ± 40 ηg/g) employing inductively coupled plasma mass spectrometry. An increase in alkaline phosphatase activity, total protein levels, and glucose concentrations was observed in urine from treated rats suggesting injury in proximal tubule cells. In parallel, histopathological studies showed tubular dilatation and cellular desquamation in these nephron segments. In summary, this study demonstrates that subcutaneous administration of TiO₂-NPs causes acute nephrotoxicity evidenced by functional and histological alterations in proximal tubule cells. This fact deserves to be mainly considered when humans are exposed directly or indirectly to TiO₂-NPs sources that cause the systemic delivery of titanium.

Keywords:

• TiO₂-NPs
• kidney
• proximal tubule cells
• nanoparticles
• rats
• nephrotoxicity

Acknowledgments

The authors thank Mrs Alejandra Martínez (Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR) for collaborating with histopathological techniques. The authors also thank Wiener Lab Argentina for analytical kits.

Disclosure statement

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

Additional information

Funding

This study was supported by the following grants: Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) [PICT 2017-N°0936], Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) [PIP 2015–2017-N°0460], and Universidad Nacional de Rosario (UNR) [PID 2020–2021].