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Updated: May 22, 2026
Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure
Published on: June 5, 2020
Gene expression in liver injury caused by long-term exposure to titanium dioxide nanoparticles in mice
Yaling Cui1, Huiting Liu, Yuguan Ze
1Medical College, Soochow University, Suzhou 215123, People's Republic of China.
Abstract:
Although liver toxicity induced by titanium dioxide nanoparticles (TiO(2) NPs) has been demonstrated, very little is known about the molecular mechanisms of multiple genes working together underlying this type of liver injury in mice. In this study, we used the whole-genome microarray analysis technique to determine the gene expression profile in the livers of mice exposed to 10 mg/kg body weight TiO(2) NPs for 90 days. The findings showed that long-term exposure to TiO(2) NPs resulted in obvious titanium accumulation in the liver and TiO(2) NP aggregation in hepatocyte nuclei, an inflammatory response, hepatocyte apoptosis, and liver dysfunction. Furthermore, microarray data showed striking changes in the expression of 785 genes related to the immune/inflammatory response, apoptosis, oxidative stress, the metabolic process, response to stress, cell cycle, ion transport, signal transduction, cell proliferation, cytoskeleton, and cell differentiation in TiO(2) NP-exposed livers. In particular, a significant reduction in complement factor D (Cfd) expression following long-term exposure to TiO(2) NPs resulted in autoimmune and inflammatory disease states in mice. Therefore, Cfd may be a potential biomarker of liver toxicity caused by TiO(2) NPs exposure.
Insights
Long-term titanium dioxide nanoparticle (TiO(2) NPs) exposure caused liver damage in mice by altering gene expression. Complement factor D (Cfd) reduction was linked to autoimmune and inflammatory responses, suggesting it as a potential toxicity biomarker.
Area of Science:
- Toxicology
- Nanotechnology
- Molecular Biology
Background:
- Titanium dioxide nanoparticles (TiO(2) NPs) are known to induce liver toxicity.
- The molecular mechanisms underlying TiO(2) NP-induced liver injury are not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms of TiO(2) NP-induced liver toxicity in mice using whole-genome microarray analysis.
- To identify key genes and pathways affected by long-term TiO(2) NP exposure.
Main Methods:
- Mice were exposed to TiO(2) NPs (10 mg/kg body weight) for 90 days.
- Whole-genome microarray analysis was performed on liver tissue.
- Titanium accumulation, NP aggregation, and liver function markers were assessed.
Main Results:
- TiO(2) NP exposure led to titanium accumulation in the liver, hepatocyte nuclear NP aggregation, inflammation, apoptosis, and liver dysfunction.
- Microarray analysis revealed significant changes in 785 genes related to immune response, apoptosis, oxidative stress, and metabolic processes.
- A notable decrease in complement factor D (Cfd) expression was observed, correlating with autoimmune and inflammatory conditions.
Conclusions:
- Long-term TiO(2) NP exposure induces significant molecular changes in the liver, contributing to toxicity.
- Reduced Cfd expression is implicated in the development of autoimmune and inflammatory liver diseases following TiO(2) NP exposure.
- Cfd may serve as a potential biomarker for TiO(2) NP-induced liver toxicity.
