Hepatic and Renal Toxicity Induced by TiO₂ Nanoparticles in Rats: A Morphological and Metabonomic Study

Abstract

Titanium dioxide (TiO2) nanoparticles (NPs) are produced abundantly and are frequently used as a white pigment in the manufacture of paints, foods, paper, and toothpaste. Despite the wide ranges of uses, there is a lack of information on the impact of NPs on animal and human health. In the present study, rats were exposed to different doses of TiO2 nanoparticles and sacrificed, respectively, 4 days, 1 month, and 2 months after treatment. Dosage of TiO2 in tissues was performed by ICP-AES and revealed an important accumulation of TiO2 in the liver. The nanoparticles induced morphological and physiological alterations in liver and kidney. In the liver, these alterations mainly affect the hepatocytes located around the centrilobular veins. These cells were the site of an oxidative stress evidenced by immunocytochemical detection of 4-hydroxynonenal (4-HNE). Kupffer cells are also the site of an important oxidative stress following the massive internalization of TiO2 nanoparticles. Enzymatic markers of liver and kidney functions (such as AST and uric acid) are also disrupted only in animals exposed to highest doses. The metabonomic approach allowed us to detect modifications in urine samples already detectable after 4 days in animals treated at the lowest dose. This metabonomic pattern testifies an oxidative stress as well as renal and hepatic alterations.

Nanoparticle-induced inflammation and fibrosis in ex vivo murine precision-cut liver slices and effects of nanoparticle exposure conditions

“…Similar to SiO 2 nanoparticles, titania (TiO 2 ) nanoparticles were selected as another well-known model nanomaterial, broadly studied in nanosafety in relation to inflammation and fibrosis (Hong and Zhang 2016 ; Suker and Jasim 2018 ; Valentini et al 2019 ). Prior to mRNA expression studies, TiO 2 nanoparticles were characterized by DLS (Supplementary Figure S11).…”

Investigating the accumulation and translocation of titanium dioxide nanoparticles with different surface modifications in static and dynamic human placental transfer models

“…NPs can accumulate in tissues over time and reach relatively high local concentrations due to their biopersistence [24,40,41]. Moreover, concentrations up to 100 µg/mL could be realistic for a potential biomedical use of TiO 2 NPs (e.g.…”

Novel Synthesis of Titanium Oxide Nanoparticles: Biological Activity and Acute Toxicity Study

“…Each blood sample was centrifuged (20 min at 4000 g ) to collect the sample serum. Liver functions (alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, albumin, alkaline phosphatase, and gamma-glutamyl transferase (GGT)), kidney functions (uric acid, creatinine, and urea), total cholesterol (high- and low-density lipoproteins), glucose, and total protein tests were determined using an automated biochemical analyzer [ 19 ].…”