Titanium Dioxide Nanoparticles Trigger Loss of Hepatic Function and Perturbation of Mitochondrial Dynamics in Primary Hepatocytes

Authors

Vaishaali Natarajan, University of Nebraska-LincolnFollow

Date of this Version

Spring 5-2015

Comments

A THESIS Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Master of Science, Major: Chemical Engineering, Under the Supervision of Professor Srivatsan Kidambi. Lincoln, Nebraska: May 2015

Copyright (c) 2015 Vaishaali Natarajan

Abstract

Titanium dioxide (TiO₂) nanoparticles are one of the most highly manufactured nanomaterials in the world with applications in copious industrial and consumer products. The liver is a major accumulation site for many nanoparticles, including TiO₂, directly through intentional ingestion or indirectly through increased environmental contamination and unintentional ingestion via water, food or animals. Growing concerns over the current usage of TiO₂ coupled with the lack of mechanistic understanding of its potential health risk is the motivation for this study. Here we determined the toxic effect of three different TiO₂ nanoparticles (commercially available rutile, anatase and P25) on primary rat hepatocytes. Specifically, we evaluated events related to hepatic functions and mitochondrial dynamics: (1) urea and albumin synthesis using colorimetric and ELISA assays, respectively; (2) redox signaling mechanisms by measuring ROS production; (3) OPA1 and Mfn-1 expression that mediates the mitochondria dynamics by PCR; and (4) mitochondrial morphology by MitoTracker Green FM staining. All three TiO₂ nanoparticles induced a significant loss in hepatic functions even at concentrations as low as 20 µg/ml with commercially used P25 causing maximum damage. TiO₂ nanoparticles induced a strong oxidative stress in primary hepatocytes.TiO₂ nanoparticles exposure also resulted in morphological changes in mitochondria and significant loss in the fusion process, thus impairing the mitochondrial dynamics. Although this study demonstrated that TiO₂ nanoparticles exposure resulted in significant damage in primary hepatocytes, more in vitro and in vivo studies are required to determine the complete toxicological mechanism on primary hepatocytes and subsequently liver function.

Adviser: Srivatsan Kidambi