Back to Journals » International Journal of Nanomedicine » Volume 14

NLRP3 inflammasome, oxidative stress, and apoptosis induced in the intestine and liver of rats treated with titanium dioxide nanoparticles: in vivo and in vitro study

Authors Abbasi-Oshaghi E, Mirzaei F, Pourjafar M

Received 26 October 2018

Accepted for publication 31 January 2019

Published 15 March 2019 Volume 2019:14 Pages 1919—1936


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Anderson Oliveira Lobo

Ebrahim Abbasi-Oshaghi,1,2,* Fatemeh Mirzaei,2,* Mona Pourjafar3

1Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; 2Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran; 3Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran

*These authors contributed equally to this work

Purpose: This study evaluated the effects of titanium dioxide nanoparticles (TiO2 NPs) on liver and intestine of normal rats.
Methods: Male rats were divided into four groups as follows: 1) control rats, 2) control rats that orally received 10 mg/kg TiO2 NPs, 3) control rats that orally received 50 mg/kg TiO2 NPs, and 4) control rats that orally received 100 mg/kg TiO2 NPs. After 30 days, the NLRP3 inflammasome pathway (NLRP3, caspase-1, and IL-1β), antioxidant pathway (superoxide dismutase [SOD], glutathione peroxidase [GPx], and catalase [CAT]), inflammatory pathway (inducible nitric oxide synthase [iNOS] and tumor necrosis factor-α [TNF-α]), and the apoptosis pathway (p53, Bax, Bcl-2, and caspase-3) were determined in the intestine and liver of the rats. H&E and Masson’s trichrome (MT) staining as well as TUNEL assay were used to examine the liver and the intestine. Biochemical factors, cytotoxicity, ROS generation, and apoptosis rate were also determined in HepG2 and Caco-2 cells.
Results: TiO2 NPs in a dose-dependent manner increased cytotoxicity, oxidative stress, and apoptosis rate in Caco-2 and HepG2 cells. The administration of TiO2 NPs significantly reduced antioxidant enzyme activity and gene expressions (SOD, CAT, and GPx) as well as glutathione (GSH) levels and total antioxidant capacity (TAC) in a dose-dependent manner. TiO2 NPs also induced the apoptosis pathway and inflammatory pathway gene expressions and caspase-3 activity in the intestine and liver. TUNEL assay was in agreement with gene expressions. TiO2 NPs also led to morphological changes in the liver and intestine.
Conclusion: TiO2 NPs could have cytotoxic effects on the intestine and liver structure and function by inducing oxidative stress, inflammation, and apoptosis.

Keywords: caco-2 cells, hepg2 cells, gene expression, rat

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]